The p97–Ataxin 3 complex regulates homeostasis of the DNA damage response E3 ubiquitin ligase RNF8

The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper‐accumulation is tumour‐promoting and positively correlates with genome instability, cancer cell invasion, metastasis and poor patient prognosis. Very little is known about the mechanisms regu...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal Vol. 38; no. 21; pp. e102361 - n/a
Main Authors: Singh, Abhay Narayan, Oehler, Judith, Torrecilla, Ignacio, Kilgas, Susan, Li, Shudong, Vaz, Bruno, Guérillon, Claire, Fielden, John, Hernandez‐Carralero, Esperanza, Cabrera, Elisa, Tullis, Iain DC, Meerang, Mayura, Barber, Paul R, Freire, Raimundo, Parsons, Jason, Vojnovic, Borivoj, Kiltie, Anne E, Mailand, Niels, Ramadan, Kristijan
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 04.10.2019
Springer Nature B.V
John Wiley and Sons Inc
Subjects:
Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
Ataxin
Ataxin 3
Ataxin-3 - genetics
Ataxin-3 - metabolism
BRCA2 protein
Breast cancer
Cancer
Cell Survival
Chromatin
Chromatin - genetics
Damage
Deactivation
Deoxyribonucleic acid
DNA
DNA Breaks, Double-Stranded
DNA damage
DNA double‐strand break repair
DNA Repair
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
E3 ubiquitin ligase RNF8
EMBO13
EMBO31
genome stability
Genomes
Genomic Instability
Genotoxicity
HEK293 Cells
HeLa Cells
Homeostasis
Homologous recombination
Homology
Humans
Inactivation
Ionizing radiation
Medical prognosis
Metastases
Non-homologous end joining
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
p97/VCP ATPase
Physiology
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Proteolysis
Recruitment
Repair
Signal Transduction
Tumors
Ubiquitin
Ubiquitin - metabolism
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
genome stability
DNA double‐strand break repair
Ataxin 3
p97/VCP ATPase
E3 ubiquitin ligase RNF8
DNA double-strand break repair
ISSN:0261-4189, 1460-2075, 1460-2075
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper‐accumulation is tumour‐promoting and positively correlates with genome instability, cancer cell invasion, metastasis and poor patient prognosis. Very little is known about the mechanisms regulating RNF8 homeostasis to preserve genome stability. Here, we identify the cellular machinery, composed of the p97/VCP ubiquitin‐dependent unfoldase/segregase and the Ataxin 3 (ATX3) deubiquitinase, which together form a physical and functional complex with RNF8 to regulate its proteasome‐dependent homeostasis under physiological conditions. Under genotoxic stress, when RNF8 is rapidly recruited to sites of DNA lesions, the p97–ATX3 machinery stimulates the extraction of RNF8 from chromatin to balance DNA repair pathway choice and promote cell survival after ionising radiation (IR). Inactivation of the p97–ATX3 complex affects the non‐homologous end joining DNA repair pathway and hypersensitises human cancer cells to IR. We propose that the p97–ATX3 complex is the essential machinery for regulation of RNF8 homeostasis under both physiological and genotoxic conditions and that targeting ATX3 may be a promising strategy to radio‐sensitise BRCA‐deficient cancers. Synopsis The RNF8 ubiquitin ligase is a key mediator of the ubiquitin‐mediated DNA damage response and regulator of double strand break repair pathway choice. Here, these roles are shown to depend on homeostatic regulation of RNF8 by the ubiquitin‐dependent segregase p97/VCP and the deubiquitinase Ataxin 3 (ATX3). A p97‐ATX3 complex maintains proteasome‐dependent RNF8 homeostasis under physiological condition. The p97‐ATX3 complex extracts RNF8 from chromatin after its recruitment to DNA damage sites. p97‐ATX3‐mediated RNF8 extraction promotes timely RNF168 recruitment and utilization of non‐homologous end joining (NHEJ) repair. Inactivation of the p97‐ATX3 complex hyper‐sensitizes BRCA2/homologous recombination‐deficient cells to ionizing radiation. Graphical Abstract Chromatin extraction of RNF8 by the ubiquitin‐dependent segregase p97/VCP and the deubiquitinase ATX3 emerges as a key mechanism for balancing DNA repair pathway choice.
AbstractList The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper‐accumulation is tumour‐promoting and positively correlates with genome instability, cancer cell invasion, metastasis and poor patient prognosis. Very little is known about the mechanisms regulating RNF8 homeostasis to preserve genome stability. Here, we identify the cellular machinery, composed of the p97/VCP ubiquitin‐dependent unfoldase/segregase and the Ataxin 3 (ATX3) deubiquitinase, which together form a physical and functional complex with RNF8 to regulate its proteasome‐dependent homeostasis under physiological conditions. Under genotoxic stress, when RNF8 is rapidly recruited to sites of DNA lesions, the p97–ATX3 machinery stimulates the extraction of RNF8 from chromatin to balance DNA repair pathway choice and promote cell survival after ionising radiation (IR). Inactivation of the p97–ATX3 complex affects the non‐homologous end joining DNA repair pathway and hypersensitises human cancer cells to IR. We propose that the p97–ATX3 complex is the essential machinery for regulation of RNF8 homeostasis under both physiological and genotoxic conditions and that targeting ATX3 may be a promising strategy to radio‐sensitise BRCA‐deficient cancers.
The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper‐accumulation is tumour‐promoting and positively correlates with genome instability, cancer cell invasion, metastasis and poor patient prognosis. Very little is known about the mechanisms regulating RNF8 homeostasis to preserve genome stability. Here, we identify the cellular machinery, composed of the p97/VCP ubiquitin‐dependent unfoldase/segregase and the Ataxin 3 (ATX3) deubiquitinase, which together form a physical and functional complex with RNF8 to regulate its proteasome‐dependent homeostasis under physiological conditions. Under genotoxic stress, when RNF8 is rapidly recruited to sites of DNA lesions, the p97–ATX3 machinery stimulates the extraction of RNF8 from chromatin to balance DNA repair pathway choice and promote cell survival after ionising radiation (IR). Inactivation of the p97–ATX3 complex affects the non‐homologous end joining DNA repair pathway and hypersensitises human cancer cells to IR. We propose that the p97–ATX3 complex is the essential machinery for regulation of RNF8 homeostasis under both physiological and genotoxic conditions and that targeting ATX3 may be a promising strategy to radio‐sensitise BRCA‐deficient cancers. Synopsis The RNF8 ubiquitin ligase is a key mediator of the ubiquitin‐mediated DNA damage response and regulator of double strand break repair pathway choice. Here, these roles are shown to depend on homeostatic regulation of RNF8 by the ubiquitin‐dependent segregase p97/VCP and the deubiquitinase Ataxin 3 (ATX3). A p97‐ATX3 complex maintains proteasome‐dependent RNF8 homeostasis under physiological condition. The p97‐ATX3 complex extracts RNF8 from chromatin after its recruitment to DNA damage sites. p97‐ATX3‐mediated RNF8 extraction promotes timely RNF168 recruitment and utilization of non‐homologous end joining (NHEJ) repair. Inactivation of the p97‐ATX3 complex hyper‐sensitizes BRCA2/homologous recombination‐deficient cells to ionizing radiation. Graphical Abstract Chromatin extraction of RNF8 by the ubiquitin‐dependent segregase p97/VCP and the deubiquitinase ATX3 emerges as a key mechanism for balancing DNA repair pathway choice.
The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper-accumulation is tumour-promoting and positively correlates with genome instability, cancer cell invasion, metastasis and poor patient prognosis. Very little is known about the mechanisms regulating RNF8 homeostasis to preserve genome stability. Here, we identify the cellular machinery, composed of the p97/VCP ubiquitin-dependent unfoldase/segregase and the Ataxin 3 (ATX3) deubiquitinase, which together form a physical and functional complex with RNF8 to regulate its proteasome-dependent homeostasis under physiological conditions. Under genotoxic stress, when RNF8 is rapidly recruited to sites of DNA lesions, the p97-ATX3 machinery stimulates the extraction of RNF8 from chromatin to balance DNA repair pathway choice and promote cell survival after ionising radiation (IR). Inactivation of the p97-ATX3 complex affects the non-homologous end joining DNA repair pathway and hypersensitises human cancer cells to IR. We propose that the p97-ATX3 complex is the essential machinery for regulation of RNF8 homeostasis under both physiological and genotoxic conditions and that targeting ATX3 may be a promising strategy to radio-sensitise BRCA-deficient cancers.The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper-accumulation is tumour-promoting and positively correlates with genome instability, cancer cell invasion, metastasis and poor patient prognosis. Very little is known about the mechanisms regulating RNF8 homeostasis to preserve genome stability. Here, we identify the cellular machinery, composed of the p97/VCP ubiquitin-dependent unfoldase/segregase and the Ataxin 3 (ATX3) deubiquitinase, which together form a physical and functional complex with RNF8 to regulate its proteasome-dependent homeostasis under physiological conditions. Under genotoxic stress, when RNF8 is rapidly recruited to sites of DNA lesions, the p97-ATX3 machinery stimulates the extraction of RNF8 from chromatin to balance DNA repair pathway choice and promote cell survival after ionising radiation (IR). Inactivation of the p97-ATX3 complex affects the non-homologous end joining DNA repair pathway and hypersensitises human cancer cells to IR. We propose that the p97-ATX3 complex is the essential machinery for regulation of RNF8 homeostasis under both physiological and genotoxic conditions and that targeting ATX3 may be a promising strategy to radio-sensitise BRCA-deficient cancers.
The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper‐accumulation is tumour‐promoting and positively correlates with genome instability, cancer cell invasion, metastasis and poor patient prognosis. Very little is known about the mechanisms regulating RNF8 homeostasis to preserve genome stability. Here, we identify the cellular machinery, composed of the p97/VCP ubiquitin‐dependent unfoldase/segregase and the Ataxin 3 (ATX3) deubiquitinase, which together form a physical and functional complex with RNF8 to regulate its proteasome‐dependent homeostasis under physiological conditions. Under genotoxic stress, when RNF8 is rapidly recruited to sites of DNA lesions, the p97–ATX3 machinery stimulates the extraction of RNF8 from chromatin to balance DNA repair pathway choice and promote cell survival after ionising radiation (IR). Inactivation of the p97–ATX3 complex affects the non‐homologous end joining DNA repair pathway and hypersensitises human cancer cells to IR. We propose that the p97–ATX3 complex is the essential machinery for regulation of RNF8 homeostasis under both physiological and genotoxic conditions and that targeting ATX3 may be a promising strategy to radio‐sensitise BRCA‐deficient cancers. Synopsis The RNF8 ubiquitin ligase is a key mediator of the ubiquitin‐mediated DNA damage response and regulator of double strand break repair pathway choice. Here, these roles are shown to depend on homeostatic regulation of RNF8 by the ubiquitin‐dependent segregase p97/VCP and the deubiquitinase Ataxin 3 (ATX3). A p97‐ATX3 complex maintains proteasome‐dependent RNF8 homeostasis under physiological condition. The p97‐ATX3 complex extracts RNF8 from chromatin after its recruitment to DNA damage sites. p97‐ATX3‐mediated RNF8 extraction promotes timely RNF168 recruitment and utilization of non‐homologous end joining (NHEJ) repair. Inactivation of the p97‐ATX3 complex hyper‐sensitizes BRCA2/homologous recombination‐deficient cells to ionizing radiation. Chromatin extraction of RNF8 by the ubiquitin‐dependent segregase p97/VCP and the deubiquitinase ATX3 emerges as a key mechanism for balancing DNA repair pathway choice.
Author Singh, Abhay Narayan
Oehler, Judith
Fielden, John
Parsons, Jason
Hernandez‐Carralero, Esperanza
Tullis, Iain DC
Kilgas, Susan
Vaz, Bruno
Cabrera, Elisa
Ramadan, Kristijan
Kiltie, Anne E
Guérillon, Claire
Barber, Paul R
Meerang, Mayura
Mailand, Niels
Freire, Raimundo
Torrecilla, Ignacio
Li, Shudong
Vojnovic, Borivoj
AuthorAffiliation 6 Universidad Fernando Pessoa Canarias Santa Maria de Guia Spain
8 Present address: Department of Biochemistry University of Oxford Oxford UK
5 Institute of Pharmacology and Toxicology‐Vetsuisse Faculty University of Zurich Zurich Switzerland
3 Unidad de Investigación Hospital Universitario de Canarias La Laguna Spain
2 Novo Nordisk Foundation Center for Protein Research University of Copenhagen Copenhagen Denmark
1 Department of Oncology Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology University of Oxford Oxford UK
4 Instituto de Tecnologías Biomédicas Universidad de La Laguna La Laguna Spain
7 Department of Molecular and Clinical Cancer Medicine Cancer Research Centre University of Liverpool Liverpool UK
9 Present address: Department of Thoracic Surgery University Hospital Zurich Zurich Switzerland
AuthorAffiliation_xml – name: 6 Universidad Fernando Pessoa Canarias Santa Maria de Guia Spain
– name: 3 Unidad de Investigación Hospital Universitario de Canarias La Laguna Spain
– name: 8 Present address: Department of Biochemistry University of Oxford Oxford UK
– name: 7 Department of Molecular and Clinical Cancer Medicine Cancer Research Centre University of Liverpool Liverpool UK
– name: 9 Present address: Department of Thoracic Surgery University Hospital Zurich Zurich Switzerland
– name: 4 Instituto de Tecnologías Biomédicas Universidad de La Laguna La Laguna Spain
– name: 5 Institute of Pharmacology and Toxicology‐Vetsuisse Faculty University of Zurich Zurich Switzerland
– name: 2 Novo Nordisk Foundation Center for Protein Research University of Copenhagen Copenhagen Denmark
– name: 1 Department of Oncology Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology University of Oxford Oxford UK
Author_xml – sequence: 1
  givenname: Abhay Narayan
  surname: Singh
  fullname: Singh, Abhay Narayan
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 2
  givenname: Judith
  surname: Oehler
  fullname: Oehler, Judith
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Department of Biochemistry, University of Oxford
– sequence: 3
  givenname: Ignacio
  surname: Torrecilla
  fullname: Torrecilla, Ignacio
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 4
  givenname: Susan
  surname: Kilgas
  fullname: Kilgas, Susan
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 5
  givenname: Shudong
  surname: Li
  fullname: Li, Shudong
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 6
  givenname: Bruno
  surname: Vaz
  fullname: Vaz, Bruno
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 7
  givenname: Claire
  surname: Guérillon
  fullname: Guérillon, Claire
  organization: Novo Nordisk Foundation Center for Protein Research, University of Copenhagen
– sequence: 8
  givenname: John
  surname: Fielden
  fullname: Fielden, John
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 9
  givenname: Esperanza
  surname: Hernandez‐Carralero
  fullname: Hernandez‐Carralero, Esperanza
  organization: Unidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas, Universidad de La Laguna
– sequence: 10
  givenname: Elisa
  surname: Cabrera
  fullname: Cabrera, Elisa
  organization: Unidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas, Universidad de La Laguna
– sequence: 11
  givenname: Iain DC
  surname: Tullis
  fullname: Tullis, Iain DC
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 12
  givenname: Mayura
  surname: Meerang
  fullname: Meerang, Mayura
  organization: Institute of Pharmacology and Toxicology‐Vetsuisse Faculty, University of Zurich, Department of Thoracic Surgery, University Hospital Zurich
– sequence: 13
  givenname: Paul R
  surname: Barber
  fullname: Barber, Paul R
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 14
  givenname: Raimundo
  surname: Freire
  fullname: Freire, Raimundo
  organization: Unidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Universidad Fernando Pessoa Canarias
– sequence: 15
  givenname: Jason
  surname: Parsons
  fullname: Parsons, Jason
  organization: Department of Molecular and Clinical Cancer Medicine, Cancer Research Centre, University of Liverpool
– sequence: 16
  givenname: Borivoj
  surname: Vojnovic
  fullname: Vojnovic, Borivoj
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 17
  givenname: Anne E
  orcidid: 0000-0001-7208-2912
  surname: Kiltie
  fullname: Kiltie, Anne E
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
– sequence: 18
  givenname: Niels
  orcidid: 0000-0002-6623-709X
  surname: Mailand
  fullname: Mailand, Niels
  organization: Novo Nordisk Foundation Center for Protein Research, University of Copenhagen
– sequence: 19
  givenname: Kristijan
  orcidid: 0000-0001-5522-021X
  surname: Ramadan
  fullname: Ramadan, Kristijan
  email: kristijan.ramadan@oncology.ox.ac.uk
  organization: Department of Oncology, Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31613024$$D View this record in MEDLINE/PubMed
BookMark eNp1kcFu1DAURS1URKeFPStkiQ2blGc7TmwJIU3LtIBKkVBZW07ykvEoidM4gXbHP_CHfAkuUzqAxMqy37lX9_kekL3e90jIUwZHTHLJX2JXbI44MM2Ai4w9IAuWZpBwyOUeWQDPWJIypffJQQgbAJAqZ4_IvmAZE8DTBaku10gHnf_49n052WvXU0FL3w0tXtMRm7m1Ewa69h36MNngAvU1naLmzcWSVrazDUYuDL4PSFeCzoW7mt0UfVrX2Pj26eJUPSYPa9sGfHJ3HpLPp6vLk7fJ-cezdyfL82QQSrOkUhIkr5RgVV1DCnmdWbAizYSqJea5rqFArlJZ5rpiteQ2K0sJdYFRyXUpDsnrre8wFx1WJfbTaFszjK6z443x1pm_J71bm8Z_MZmKP6V5NHhxZzD6qxnDZDoXSmxb26Ofg-ECZK51pkVEn_-Dbvw89nG9SDGW5ilIGalnfya6j_K7gAi82gJfXYs393MG5lfB5rZgsyvYrD4cv99do5xt5SEq-wbHXYr_WYif-airhQ
ContentType Journal Article
Copyright The Author(s) 2019
2019 The Authors. Published under the terms of the CC BY 4.0 license
2019 The Authors. Published under the terms of the CC BY 4.0 license.
2019 EMBO
Copyright_xml – notice: The Author(s) 2019
– notice: 2019 The Authors. Published under the terms of the CC BY 4.0 license
– notice: 2019 The Authors. Published under the terms of the CC BY 4.0 license.
– notice: 2019 EMBO
DBID C6C
24P
CGR
CUY
CVF
ECM
EIF
NPM
7QG
7QL
7QP
7T5
7TK
7TM
7TO
7U9
8FD
C1K
FR3
H94
K9.
M7N
P64
RC3
7X8
5PM
DOI 10.15252/embj.2019102361
DatabaseName Springer Nature OA Free Journals
Wiley Online Library Open Access
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Animal Behavior Abstracts
Bacteriology Abstracts (Microbiology B)
Calcium & Calcified Tissue Abstracts
Immunology Abstracts
Neurosciences Abstracts
Nucleic Acids Abstracts
Oncogenes and Growth Factors Abstracts
Virology and AIDS Abstracts
Technology Research Database
Environmental Sciences and Pollution Management
Engineering Research Database
AIDS and Cancer Research Abstracts
ProQuest Health & Medical Complete (Alumni)
Algology Mycology and Protozoology Abstracts (Microbiology C)
Biotechnology and BioEngineering Abstracts
Genetics Abstracts
MEDLINE - Academic
PubMed Central (Full Participant titles)
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Virology and AIDS Abstracts
Oncogenes and Growth Factors Abstracts
Technology Research Database
Nucleic Acids Abstracts
ProQuest Health & Medical Complete (Alumni)
Neurosciences Abstracts
Biotechnology and BioEngineering Abstracts
Environmental Sciences and Pollution Management
Genetics Abstracts
Animal Behavior Abstracts
Bacteriology Abstracts (Microbiology B)
Algology Mycology and Protozoology Abstracts (Microbiology C)
AIDS and Cancer Research Abstracts
Immunology Abstracts
Engineering Research Database
Calcium & Calcified Tissue Abstracts
MEDLINE - Academic
DatabaseTitleList Virology and AIDS Abstracts

MEDLINE
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: 24P
  name: Wiley Open Access
  url: https://authorservices.wiley.com/open-science/open-access/browse-journals.html
  sourceTypes: Publisher
– sequence: 2
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Chemistry
Biology
DocumentTitleAlternate Abhay Narayan Singh et al
EISSN 1460-2075
EndPage n/a
ExternalDocumentID PMC6826192
31613024
EMBJ2019102361
10_15252_embj_2019102361
Genre article
Research Support, Non-U.S. Gov't
Journal Article
GrantInformation_xml – fundername: Swiss National Science Foundation
  grantid: 31003A_141197
  funderid: 10.13039/501100001711
– fundername: UK Research and Innovation | Medical Research Council (MRC)
  grantid: MC_EX_MR/K022830/1
  funderid: 10.13039/501100000265
– fundername: Cancer Research UK (CRUK)
  grantid: C5255/A15935
  funderid: 10.13039/501100000289
– fundername: Kræftens Bekæmpelse (Danish Cancer Society)
  grantid: R146-RP11394
  funderid: 10.13039/100008363
– fundername: Spanish Ministry of Science and Universities
  grantid: SAF2016-80626-R
– fundername: Swiss National Science Foundation
  funderid: 31003A_141197
– fundername: Kræftens Bekæmpelse (Danish Cancer Society)
  funderid: R146-RP11394
– fundername: Spanish Ministry of Science and Universities
  funderid: SAF2016-80626-R
– fundername: UK Research and Innovation | Medical Research Council (MRC)
  funderid: MC_EX_MR/K022830/1
– fundername: Cancer Research UK (CRUK)
  funderid: C5255/A15935
– fundername: Medical Research Council
  grantid: MC_UU_00001/1
– fundername: Medical Research Council
  grantid: MC_EX_MR/K022830/1
– fundername: Medical Research Council
  grantid: MR/M000354/1
– fundername: Cancer Research UK
  grantid: 23279
– fundername: Swiss National Science Foundation
  grantid: 31003A_141197
– fundername: Cancer Research UK
  grantid: 15677
– fundername: Cancer Research UK (CRUK)
  grantid: C5255/A15935
– fundername: Kræftens Bekæmpelse (Danish Cancer Society)
  grantid: R146-RP11394
– fundername: UK Research and Innovation | Medical Research Council (MRC)
  grantid: MC_EX_MR/K022830/1
GroupedDBID ---
-DZ
-Q-
-~X
0R~
123
1OC
24P
29G
2WC
33P
36B
39C
53G
5VS
70F
8R4
8R5
A8Z
AAESR
AAEVG
AAHBH
AAHHS
AAIHA
AAJSJ
AANLZ
AAONW
AASGY
AAXRX
AAYCA
AAZKR
ABCUV
ABLJU
ACAHQ
ACCFJ
ACCZN
ACGFO
ACGFS
ACNCT
ACPOU
ACPRK
ACXBN
ACXQS
ADBBV
ADEOM
ADKYN
ADMGS
ADOZA
ADXAS
ADZMN
AEEZP
AEGXH
AEIGN
AENEX
AEQDE
AEUYR
AFBPY
AFFNX
AFGKR
AFPWT
AFRAH
AFWVQ
AFZJQ
AHMBA
AIAGR
AIURR
AIWBW
AJBDE
ALAGY
ALIPV
ALMA_UNASSIGNED_HOLDINGS
ALUQN
AMBMR
AMYDB
AOIJS
AUFTA
AZBYB
AZFZN
AZVAB
BAWUL
BDRZF
BENPR
BFHJK
BMNLL
BMXJE
BRXPI
BTFSW
C6C
CS3
DCZOG
DIK
DPXWK
DRFUL
DRSTM
DU5
E3Z
EBD
EBLON
EBS
EMB
EMOBN
F5P
G-S
GROUPED_DOAJ
GX1
HH5
HK~
HYE
KQ8
LATKE
LEEKS
LITHE
LOXES
LUTES
LYRES
MEWTI
MRFUL
MRSTM
MSFUL
MSSTM
MVM
MXFUL
MXSTM
MY~
O9-
OK1
P2P
P2W
Q2X
R.K
RHF
RHI
RNS
ROL
RPM
SV3
TN5
TR2
WBKPD
WH7
WIH
WIK
WIN
WOHZO
WXSBR
WYJ
YSK
ZCA
ZZTAW
~KM
ABJNI
AAMMB
AASML
ABZEH
AEFGJ
AGXDD
AIDQK
AIDYY
CGR
CUY
CVF
ECM
EIF
EJD
NAO
NPM
7QG
7QL
7QP
7T5
7TK
7TM
7TO
7U9
8FD
AJAOE
C1K
ESTFP
FR3
H94
K9.
M7N
P64
RC3
7X8
5PM
ID FETCH-LOGICAL-p3891-d85052d831dff0407f6a0a34638f5e779f0be2845c79d1f52a6cc50fbed8529c3
IEDL.DBID 24P
ISICitedReferencesCount 45
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000489982500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 0261-4189
1460-2075
IngestDate Tue Sep 30 16:47:15 EDT 2025
Sat Sep 27 23:11:24 EDT 2025
Mon Oct 06 17:43:42 EDT 2025
Mon Jul 21 05:42:53 EDT 2025
Wed Jan 22 16:39:13 EST 2025
Fri Feb 21 02:37:31 EST 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 21
Keywords genome stability
DNA double‐strand break repair
Ataxin 3
p97/VCP ATPase
E3 ubiquitin ligase RNF8
DNA double-strand break repair
Language English
License Attribution
2019 The Authors. Published under the terms of the CC BY 4.0 license.
This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-p3891-d85052d831dff0407f6a0a34638f5e779f0be2845c79d1f52a6cc50fbed8529c3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
These authors contributed equally to this work
ORCID 0000-0001-7208-2912
0000-0001-5522-021X
0000-0002-6623-709X
OpenAccessLink https://onlinelibrary.wiley.com/doi/abs/10.15252%2Fembj.2019102361
PMID 31613024
PQID 2311474055
PQPubID 35985
PageCount 25
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_6826192
proquest_miscellaneous_2305799693
proquest_journals_2311474055
pubmed_primary_31613024
wiley_primary_10_15252_embj_2019102361_EMBJ2019102361
springer_journals_10_15252_embj_2019102361
PublicationCentury 2000
PublicationDate 2019-10-04
PublicationDateYYYYMMDD 2019-10-04
PublicationDate_xml – month: 10
  year: 2019
  text: 2019-10-04
  day: 04
PublicationDecade 2010
PublicationPlace London
PublicationPlace_xml – name: London
– name: England
– name: New York
– name: Hoboken
PublicationTitle The EMBO journal
PublicationTitleAbbrev EMBO J
PublicationTitleAlternate EMBO J
PublicationYear 2019
Publisher Nature Publishing Group UK
Springer Nature B.V
John Wiley and Sons Inc
Publisher_xml – name: Nature Publishing Group UK
– name: Springer Nature B.V
– name: John Wiley and Sons Inc
References Jeggo, Lobrich (CR34) 2015; 471
Zong, Adam, Wang, Sasanuma, Callen, Murga, Day, Kruhlak, Wong, Munro (CR86) 2019; 73
Ackermann, Schell, Pokrzywa, Kevei, Gartner, Schumacher, Hoppe (CR1) 2016; 23
Livingstone, Ruan, Weiner, Clauser, Strack, Jin, Williams, Greulich, Gardner, Venere (CR42) 2005; 65
Puumalainen, Lessel, Ruthemann, Kaczmarek, Bachmann, Ramadan, Naegeli (CR62) 2014; 5
Stewart, Stankovic, Byrd, Wechsler, Miller, Huissoon, Drayson, West, Elledge, Taylor (CR68) 2007; 104
Jeggo, Geuting, Lobrich (CR33) 2011; 101
Zhao, Mudge, Soll, Rodrigues, Byrum, Schwarzkopf, Bradstreet, Gygi, Edelson, Mosammaparast (CR81) 2018; 69
Mattiroli, Vissers, van Dijk, Ikpa, Citterio, Vermeulen, Marteijn, Sixma (CR49) 2012; 150
Bennardo, Cheng, Huang, Stark (CR5) 2008; 4
Bodnar, Rapoport (CR8) 2017; 169
Doil, Mailand, Bekker‐Jensen, Menard, Larsen, Pepperkok, Ellenberg, Panier, Durocher, Bartek (CR24) 2009; 136
Magnaghi, D'Alessio, Valsasina, Avanzi, Rizzi, Asa, Gasparri, Cozzi, Cucchi, Orrenius (CR45) 2013; 9
Munoz, Laulier, Gunn, Cheng, Robbiani, Nussenzweig, Stark (CR54) 2012; 287
Zimmer, Tacconi, Folio, Badie, Porru, Klare, Tumiati, Markkanen, Halder, Ryan (CR85) 2016; 61
Wang, Li, Ye (CR75) 2006; 174
Zhu, Sharma, He, Wani, Wani (CR84) 2015; 14
Zhang, Zhou, Sarkeshik, Yates, Thomson, Zhang, Lee, Lee (CR80) 2013; 288
Panier, Durocher (CR58) 2013; 14
Kolas, Chapman, Nakada, Ylanko, Chahwan, Sweeney, Panier, Mendez, Wildenhain, Thomson (CR37) 2007; 318
Clouaire, Rocher, Lashgari, Arnould, Aguirrebengoa, Biernacka, Skrzypczak, Aymard, Fongang, Dojer (CR18) 2018; 72
Meyer, Weihl (CR53) 2014; 127
Chapman, Taylor, Boulton (CR15) 2012; 47
Cuella‐Martin, Oliveira, Lockstone, Snellenberg, Grolmusova, Chapman (CR20) 2016; 64
Collins, Goldberg (CR19) 2017; 169
Meerang, Ritz, Paliwal, Garajova, Bosshard, Mailand, Janscak, Hubscher, Meyer, Ramadan (CR50) 2011; 13
Feng, Chen (CR26) 2012; 19
Dev, Chiang, Lescale, de Krijger, Martin, Pilger, Coates, Sczaniecka‐Clift, Wei, Ostermaier (CR23) 2018; 20
Paul, Wang (CR59) 2017; 66
Jeggo, Pearl, Carr (CR35) 2016; 16
Zhong, Pittman (CR82) 2006; 15
Stewart, Panier, Townsend, Al‐Hakim, Kolas, Miller, Nakada, Ylanko, Olivarius, Mendez (CR69) 2009; 136
Acs, Luijsterburg, Ackermann, Salomons, Hoppe, Dantuma (CR2) 2011; 18
Chang, Pannunzio, Adachi, Lieber (CR14) 2017; 18
Jackson, Bartek (CR32) 2009; 461
Mailand, Bekker‐Jensen, Faustrup, Melander, Bartek, Lukas, Lukas (CR46) 2007; 131
Mendez, Stillman (CR51) 2000; 20
Vaz, Popovic, Newman, Fielden, Aitkenhead, Halder, Singh, Vendrell, Fischer, Torrecilla (CR74) 2016; 64
Nickson, Moori, Carter, Rubbi, Parsons (CR56) 2017; 8
Ye, Meyer, Rapoport (CR79) 2003; 162
Carter, Nickson, Thompson, Kacperek, Hill, Parsons (CR13) 2018; 100
Lee, Li, Ruan, Powers, Thompson, Frohman, Chan (CR40) 2016; 63
Strickfaden, McDonald, Kruhlak, Haince, Th'ng, Rouleau, Ishibashi, Corry, Ausio, Underhill (CR70) 2016; 291
Wang, Elledge (CR76) 2007; 104
Sobhian, Shao, Lilli, Culhane, Moreau, Xia, Livingston, Greenberg (CR67) 2007; 316
Kuang, Li, Guo, Su, Wang, Xu, Wang, Meng, Lei, Xu (CR38) 2016; 35
Bergink, Ammon, Kern, Schermelleh, Leonhardt, Jentsch (CR6) 2013; 15
Lok, Sy, Dong, Ching, Tsao, Thomson, Huen (CR43) 2012; 40
Ritz, Vuk, Kirchner, Bug, Schutz, Hayer, Bremer, Lusk, Baloh, Lee (CR65) 2011; 13
Matos, Nobrega, Louros, Almeida, Ferreiro, Valero, Pereira de Almeida, Macedo‐Ribeiro, Carvalho (CR48) 2016; 212
Sellou, Lebeaupin, Chapuis, Smith, Hegele, Singh, Kozlowski, Bultmann, Ladurner, Timinszky (CR66) 2016; 27
Ramadan (CR63) 2012; 11
Chou, Bulfer, Weihl, Li, Lis, Walters, Schoenen, Lin, Deshaies, Arkin (CR17) 2014; 426
Friedberg, Aguilera, Gellert, Hanawalt, Hays, Lehmann, Lindahl, Lowndes, Sarasin, Wood (CR27) 2006; 5
Aparicio, Baer, Gautier (CR3) 2014; 19
Lee, Ruan, He, Chan (CR41) 2016; 3
Bodnar, Rapoport (CR7) 2017; 6
Baranes‐Bachar, Levy‐Barda, Oehler, Reid, Soria‐Bretones, Voss, Chung, Park, Liu, Yoon (CR4) 2018; 69
Noordermeer, Adam, Setiaputra, Barazas, Pettitt, Ling, Olivieri, Alvarez‐Quilon, Moatti, Zimmermann (CR57) 2018; 560
Bug, Meyer (CR11) 2012; 179
Laco, Cortes, Travis, Paulson, Rego (CR39) 2012; 7
Meyer, Bug, Bremer (CR52) 2012; 14
Gudjonsson, Altmeyer, Savic, Toledo, Dinant, Grofte, Bartkova, Poulsen, Oka, Bekker‐Jensen (CR29) 2012; 150
Buchberger, Schindelin, Hanzelmann (CR10) 2015; 589
Thorslund, Ripplinger, Hoffmann, Wild, Uckelmann, Villumsen, Narita, Sixma, Choudhary, Bekker‐Jensen (CR72) 2015; 527
Gatti, Pinato, Maiolica, Rocchio, Prato, Aebersold, Penengo (CR28) 2015; 10
Sy, Jiang, Dong, Lok, Wu, Cai, Yeung, Huang, Chen, Deng (CR71) 2011; 286
Luijsterburg, Acs, Ackermann, Wiegant, Bekker‐Jensen, Larsen, Khanna, van Attikum, Mailand, Dantuma (CR44) 2012; 31
Rao, Williams, Cocklin, Loll (CR64) 2017; 292
Watanabe, Watanabe, Akimov, Bartkova, Blagoev, Lukas, Bartek (CR77) 2013; 20
Pinato, Scandiuzzi, Arnaudo, Citterio, Gaudino, Penengo (CR61) 2009; 10
Vaz, Halder, Ramadan (CR73) 2013; 4
Kim, Chen, Yu (CR36) 2007; 316
Doss‐Pepe, Stenroos, Johnson, Madura (CR25) 2003; 23
Burnett, Li, Pittman (CR12) 2003; 12
Chou, Brown, Minond, Nordin, Li, Jones, Chase, Porubsky, Stoltz, Schoenen (CR16) 2011; 108
Mallette, Mattiroli, Cui, Young, Hendzel, Mer, Sixma, Richard (CR47) 2012; 31
Nakada, Yonamine, Matsuo (CR55) 2012; 72
van den Boom, Wolf, Weimann, Schulze, Li, Kaschani, Riemer, Zierhut, Kaiser, Iliakis (CR9) 2016; 64
Hustedt, Durocher (CR31) 2016; 19
Hodge, Ismail, Edwards, Hura, Xiao, Tainer, Hendzel, Glover (CR30) 2016; 291
Zhou, Wang, Yao, Wong, Djakovic, Kumar, Rice, Valle, Soriano, Menon (CR83) 2015; 58
Dantuma, Acs, Luijsterburg (CR22) 2014; 329
Winborn, Travis, Todi, Scaglione, Xu, Williams, Cohen, Peng, Paulson (CR78) 2008; 283
Dantuma, Groothuis, Salomons, Neefjes (CR21) 2006; 173
Pfeiffer, Luijsterburg, Acs, Wiegant, Helfricht, Herzog, Minoia, Bottcher, Salomons, van Attikum (CR60) 2017; 36
2018; 560
2007; 104
2017a; 6
2017; 8
2012; 287
2013; 4
2015; 589
2013; 20
2006; 174
2013; 288
2006; 173
2012; 19
2005; 65
2011; 13
2008; 4
2012; 14
2011; 18
2012; 11
2016; 35
2013; 9
2003; 12
2016a; 63
2012; 72
2014; 127
2013; 15
2014; 5
2013; 14
2014; 329
2016b; 3
2009; 10
2012; 179
2017; 36
2007; 131
2003; 162
2014; 19
2018; 72
2017; 169
2011; 286
2018; 100
2015; 58
2015; 14
2019; 73
2016; 19
2017; 66
2015; 10
2000; 20
2006; 15
2006; 5
2017; 292
2015; 527
2017b; 169
2016; 16
2018; 20
2009; 136
2012; 31
2008; 283
2018; 69
2014; 426
2012; 150
2015; 471
2007; 316
2011; 108
2016; 212
2016; 64
2016; 61
2017; 18
2009; 461
2012; 47
2016; 291
2012; 7
2007; 318
2016; 27
2011; 101
2016; 23
2003; 23
2012; 40
References_xml – volume: 20
  start-page: 8602
  year: 2000
  end-page: 8612
  ident: CR51
  article-title: Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis
  publication-title: Mol Cell Biol
– volume: 127
  start-page: 3877
  year: 2014
  end-page: 3883
  ident: CR53
  article-title: The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis
  publication-title: J Cell Sci
– volume: 150
  start-page: 697
  year: 2012
  end-page: 709
  ident: CR29
  article-title: TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes
  publication-title: Cell
– volume: 27
  start-page: 3791
  year: 2016
  end-page: 3799
  ident: CR66
  article-title: The poly(ADP‐ribose)‐dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage
  publication-title: Mol Biol Cell
– volume: 212
  start-page: 465
  year: 2016
  end-page: 480
  ident: CR48
  article-title: Ataxin‐3 phosphorylation decreases neuronal defects in spinocerebellar ataxia type 3 models
  publication-title: J Cell Biol
– volume: 179
  start-page: 78
  year: 2012
  end-page: 82
  ident: CR11
  article-title: Expanding into new markets–VCP/p97 in endocytosis and autophagy
  publication-title: J Struct Biol
– volume: 291
  start-page: 9396
  year: 2016
  end-page: 9410
  ident: CR30
  article-title: RNF8 E3 ubiquitin ligase stimulates Ubc13 E2 conjugating activity that is essential for DNA double strand break signaling and BRCA1 tumor suppressor recruitment
  publication-title: J Biol Chem
– volume: 23
  start-page: 995
  year: 2016
  end-page: 1002
  ident: CR1
  article-title: E4 ligase‐specific ubiquitination hubs coordinate DNA double‐strand‐break repair and apoptosis
  publication-title: Nat Struct Mol Biol
– volume: 13
  start-page: 1376
  year: 2011
  end-page: 1382
  ident: CR50
  article-title: The ubiquitin‐selective segregase VCP/p97 orchestrates the response to DNA double‐strand breaks
  publication-title: Nat Cell Biol
– volume: 150
  start-page: 1182
  year: 2012
  end-page: 1195
  ident: CR49
  article-title: RNF168 ubiquitinates K13‐15 on H2A/H2AX to drive DNA damage signaling
  publication-title: Cell
– volume: 104
  start-page: 16910
  year: 2007
  end-page: 16915
  ident: CR68
  article-title: RIDDLE immunodeficiency syndrome is linked to defects in 53BP1‐mediated DNA damage signaling
  publication-title: Proc Natl Acad Sci USA
– volume: 3
  start-page: e1242454
  year: 2016
  ident: CR41
  article-title: Two‐faced activity of RNF8: what “twists” it from a genome guardian to a cancer facilitator?
  publication-title: Mol Cell Oncol
– volume: 10
  start-page: 55
  year: 2009
  ident: CR61
  article-title: RNF168, a new RING finger, MIU‐containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX
  publication-title: BMC Mol Biol
– volume: 589
  start-page: 2578
  year: 2015
  end-page: 2589
  ident: CR10
  article-title: Control of p97 function by cofactor binding
  publication-title: FEBS Lett
– volume: 329
  start-page: 9
  year: 2014
  end-page: 17
  ident: CR22
  article-title: Should I stay or should I go: VCP/p97‐mediated chromatin extraction in the DNA damage response
  publication-title: Exp Cell Res
– volume: 316
  start-page: 1198
  year: 2007
  end-page: 1202
  ident: CR67
  article-title: RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites
  publication-title: Science
– volume: 101
  start-page: 7
  year: 2011
  end-page: 12
  ident: CR33
  article-title: The role of homologous recombination in radiation‐induced double‐strand break repair
  publication-title: Radiother Oncol
– volume: 4
  start-page: e1000110
  year: 2008
  ident: CR5
  article-title: Alternative‐NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair
  publication-title: PLoS Genet
– volume: 19
  start-page: 201
  year: 2012
  end-page: 206
  ident: CR26
  article-title: The E3 ligase RNF8 regulates KU80 removal and NHEJ repair
  publication-title: Nat Struct Mol Biol
– volume: 5
  start-page: 986
  year: 2006
  end-page: 996
  ident: CR27
  article-title: DNA repair: from molecular mechanism to human disease
  publication-title: DNA Repair (Amst)
– volume: 291
  start-page: 1789
  year: 2016
  end-page: 1802
  ident: CR70
  article-title: Poly(ADP‐ribosyl)ation‐dependent transient chromatin decondensation and histone displacement following laser microirradiation
  publication-title: J Biol Chem
– volume: 20
  start-page: 1425
  year: 2013
  end-page: 1433
  ident: CR77
  article-title: JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1‐mediated chromatin response to DNA breaks
  publication-title: Nat Struct Mol Biol
– volume: 14
  start-page: 1413
  year: 2015
  end-page: 1425
  ident: CR84
  article-title: USP7 deubiquitinase promotes ubiquitin‐dependent DNA damage signaling by stabilizing RNF168
  publication-title: Cell Cycle
– volume: 61
  start-page: 449
  year: 2016
  end-page: 460
  ident: CR85
  article-title: Targeting BRCA1 and BRCA2 deficiencies with G‐quadruplex‐interacting compounds
  publication-title: Mol Cell
– volume: 18
  start-page: 1345
  year: 2011
  end-page: 1350
  ident: CR2
  article-title: The AAA‐ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double‐strand breaks
  publication-title: Nat Struct Mol Biol
– volume: 5
  start-page: 3695
  year: 2014
  ident: CR62
  article-title: Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity
  publication-title: Nat Commun
– volume: 287
  start-page: 40618
  year: 2012
  end-page: 40628
  ident: CR54
  article-title: RING finger nuclear factor RNF168 is important for defects in homologous recombination caused by loss of the breast cancer susceptibility factor BRCA1
  publication-title: J Biol Chem
– volume: 69
  start-page: 866
  year: 2018
  end-page: 878
  ident: CR4
  article-title: The ubiquitin E3/E4 ligase UBE4A adjusts protein ubiquitylation and accumulation at sites of DNA damage. Facilitating double‐strand break repair
  publication-title: Mol Cell
– volume: 461
  start-page: 1071
  year: 2009
  end-page: 1078
  ident: CR32
  article-title: The DNA‐damage response in human biology and disease
  publication-title: Nature
– volume: 72
  start-page: 250
  year: 2018
  end-page: 262
  ident: CR18
  article-title: Comprehensive mapping of histone modifications at DNA double‐strand breaks deciphers repair pathway chromatin signatures
  publication-title: Mol Cell
– volume: 108
  start-page: 4834
  year: 2011
  end-page: 4839
  ident: CR16
  article-title: Reversible inhibitor of p97, DBeQ, impairs both ubiquitin‐dependent and autophagic protein clearance pathways
  publication-title: Proc Natl Acad Sci USA
– volume: 35
  start-page: 88
  year: 2016
  ident: CR38
  article-title: RNF8 promotes epithelial‐mesenchymal transition of breast cancer cells
  publication-title: J Exp Clin Cancer Res
– volume: 318
  start-page: 1637
  year: 2007
  end-page: 1640
  ident: CR37
  article-title: Orchestration of the DNA‐damage response by the RNF8 ubiquitin ligase
  publication-title: Science
– volume: 31
  start-page: 2511
  year: 2012
  end-page: 2527
  ident: CR44
  article-title: A new non‐catalytic role for ubiquitin ligase RNF8 in unfolding higher‐order chromatin structure
  publication-title: EMBO J
– volume: 471
  start-page: 1
  year: 2015
  end-page: 11
  ident: CR34
  article-title: How cancer cells hijack DNA double‐strand break repair pathways to gain genomic instability
  publication-title: Biochem J
– volume: 292
  start-page: 18392
  year: 2017
  end-page: 18407
  ident: CR64
  article-title: Interaction between the AAA(+) ATPase p97 and its cofactor ataxin3 in health and disease: nucleotide‐induced conformational changes regulate cofactor binding
  publication-title: J Biol Chem
– volume: 19
  start-page: 169
  year: 2014
  end-page: 175
  ident: CR3
  article-title: DNA double‐strand break repair pathway choice and cancer
  publication-title: DNA Repair (Amst)
– volume: 100
  start-page: 776
  year: 2018
  end-page: 784
  ident: CR13
  article-title: Complex DNA damage induced by high linear energy transfer alpha‐particles and protons triggers a specific cellular DNA damage response
  publication-title: Int J Radiat Oncol Biol Phys
– volume: 40
  start-page: 196
  year: 2012
  end-page: 205
  ident: CR43
  article-title: Differential regulation of RNF8‐mediated Lys48‐ and Lys63‐based poly‐ubiquitylation
  publication-title: Nucleic Acids Res
– volume: 162
  start-page: 71
  year: 2003
  end-page: 84
  ident: CR79
  article-title: Function of the p97‐Ufd1‐Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains
  publication-title: J Cell Biol
– volume: 58
  start-page: 9480
  year: 2015
  end-page: 9497
  ident: CR83
  article-title: Discovery of a first‐in‐class, potent, selective, and orally bioavailable inhibitor of the p97 AAA ATPase (CB‐5083)
  publication-title: J Med Chem
– volume: 283
  start-page: 26436
  year: 2008
  end-page: 26443
  ident: CR78
  article-title: The deubiquitinating enzyme ataxin‐3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains
  publication-title: J Biol Chem
– volume: 136
  start-page: 420
  year: 2009
  end-page: 434
  ident: CR69
  article-title: The RIDDLE syndrome protein mediates a ubiquitin‐dependent signaling cascade at sites of DNA damage
  publication-title: Cell
– volume: 36
  start-page: 1066
  year: 2017
  end-page: 1083
  ident: CR60
  article-title: Ataxin‐3 consolidates the MDC1‐dependent DNA double‐strand break response by counteracting the SUMO‐targeted ubiquitin ligase RNF4
  publication-title: EMBO J
– volume: 64
  start-page: 189
  year: 2016
  end-page: 198
  ident: CR9
  article-title: VCP/p97 extracts sterically trapped Ku70/80 rings from DNA in Double‐strand break repair
  publication-title: Mol Cell
– volume: 12
  start-page: 3195
  year: 2003
  end-page: 3205
  ident: CR12
  article-title: The polyglutamine neurodegenerative protein ataxin‐3 binds polyubiquitylated proteins and has ubiquitin protease activity
  publication-title: Hum Mol Genet
– volume: 15
  start-page: 2409
  year: 2006
  end-page: 2420
  ident: CR82
  article-title: Ataxin‐3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates
  publication-title: Hum Mol Genet
– volume: 173
  start-page: 19
  year: 2006
  end-page: 26
  ident: CR21
  article-title: A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin remodeling
  publication-title: J Cell Biol
– volume: 286
  start-page: 22355
  year: 2011
  end-page: 22361
  ident: CR71
  article-title: Critical roles of ring finger protein RNF8 in replication stress responses
  publication-title: J Biol Chem
– volume: 174
  start-page: 963
  year: 2006
  end-page: 971
  ident: CR75
  article-title: Regulation of retrotranslocation by p97‐associated deubiquitinating enzyme ataxin‐3
  publication-title: J Cell Biol
– volume: 7
  start-page: e43563
  year: 2012
  ident: CR39
  article-title: Valosin‐containing protein (VCP/p97) is an activator of wild‐type ataxin‐3
  publication-title: PLoS ONE
– volume: 426
  start-page: 2886
  year: 2014
  end-page: 2899
  ident: CR17
  article-title: Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains
  publication-title: J Mol Biol
– volume: 65
  start-page: 7533
  year: 2005
  end-page: 7540
  ident: CR42
  article-title: Valosin‐containing protein phosphorylation at Ser784 in response to DNA damage
  publication-title: Can Res
– volume: 20
  start-page: 954
  year: 2018
  end-page: 965
  ident: CR23
  article-title: Shieldin complex promotes DNA end‐joining and counters homologous recombination in BRCA1‐null cells
  publication-title: Nat Cell Biol
– volume: 560
  start-page: 117
  year: 2018
  end-page: 121
  ident: CR57
  article-title: The shieldin complex mediates 53BP1‐dependent DNA repair
  publication-title: Nature
– volume: 18
  start-page: 495
  year: 2017
  end-page: 506
  ident: CR14
  article-title: Non‐homologous DNA end joining and alternative pathways to double‐strand break repair
  publication-title: Nat Rev Mol Cell Biol
– volume: 31
  start-page: 1865
  year: 2012
  end-page: 1878
  ident: CR47
  article-title: RNF8‐ and RNF168‐dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites
  publication-title: EMBO J
– volume: 288
  start-page: 2941
  year: 2013
  end-page: 2950
  ident: CR80
  article-title: Identification of RNF8 as a ubiquitin ligase involved in targeting the p12 subunit of DNA polymerase delta for degradation in response to DNA damage
  publication-title: J Biol Chem
– volume: 136
  start-page: 435
  year: 2009
  end-page: 446
  ident: CR24
  article-title: RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins
  publication-title: Cell
– volume: 19
  start-page: 1
  year: 2016
  end-page: 9
  ident: CR31
  article-title: The control of DNA repair by the cell cycle
  publication-title: Nat Cell Biol
– volume: 169
  start-page: 722
  year: 2017
  end-page: 735
  ident: CR8
  article-title: Molecular mechanism of substrate processing by the Cdc48 ATPase complex
  publication-title: Cell
– volume: 66
  start-page: 458
  year: 2017
  end-page: 472
  ident: CR59
  article-title: RNF8‐ and Ube2S‐dependent ubiquitin lysine 11‐linkage modification in response to DNA damage
  publication-title: Mol Cell
– volume: 69
  start-page: 505
  year: 2018
  end-page: 516
  ident: CR81
  article-title: OTUD4 is a phospho‐activated K63 deubiquitinase that regulates MyD88‐dependent signaling
  publication-title: Mol Cell
– volume: 131
  start-page: 887
  year: 2007
  end-page: 900
  ident: CR46
  article-title: RNF8 ubiquitylates histones at DNA double‐strand breaks and promotes assembly of repair proteins
  publication-title: Cell
– volume: 169
  start-page: 792
  year: 2017
  end-page: 806
  ident: CR19
  article-title: The logic of the 26S proteasome
  publication-title: Cell
– volume: 23
  start-page: 6469
  year: 2003
  end-page: 6483
  ident: CR25
  article-title: Ataxin‐3 interactions with rad23 and valosin‐containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin‐mediated proteolysis
  publication-title: Mol Cell Biol
– volume: 16
  start-page: 35
  year: 2016
  end-page: 42
  ident: CR35
  article-title: DNA repair, genome stability and cancer: a historical perspective
  publication-title: Nat Rev Cancer
– volume: 63
  start-page: 1021
  year: 2016
  end-page: 1033
  ident: CR40
  article-title: The DNA damage transducer RNF8 facilitates cancer chemoresistance and progression through twist activation
  publication-title: Mol Cell
– volume: 11
  start-page: 1062
  year: 2012
  end-page: 1069
  ident: CR63
  article-title: p97/VCP‐ and Lys48‐linked polyubiquitination form a new signaling pathway in DNA damage response
  publication-title: Cell Cycle
– volume: 316
  start-page: 1202
  year: 2007
  end-page: 1205
  ident: CR36
  article-title: Ubiquitin‐binding protein RAP80 mediates BRCA1‐dependent DNA damage response
  publication-title: Science
– volume: 6
  start-page: 1318
  year: 2017
  ident: CR7
  article-title: Toward an understanding of the Cdc48/p97 ATPase
  publication-title: F1000Res
– volume: 73
  start-page: 1267
  year: 2019
  end-page: 1281
  ident: CR86
  article-title: BRCA1 haploinsufficiency is masked by RNF168‐mediated chromatin ubiquitylation
  publication-title: Mol Cell
– volume: 4
  start-page: 60
  year: 2013
  ident: CR73
  article-title: Role of p97/VCP (Cdc48) in genome stability
  publication-title: Front Genet
– volume: 8
  start-page: 29963
  year: 2017
  end-page: 29975
  ident: CR56
  article-title: Misregulation of DNA damage repair pathways in HPV‐positive head and neck squamous cell carcinoma contributes to cellular radiosensitivity
  publication-title: Oncotarget
– volume: 64
  start-page: 51
  year: 2016
  end-page: 64
  ident: CR20
  article-title: 53BP1 integrates DNA repair and p53‐dependent cell fate decisions via distinct mechanisms
  publication-title: Mol Cell
– volume: 10
  start-page: 226
  year: 2015
  end-page: 238
  ident: CR28
  article-title: RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage
  publication-title: Cell Rep
– volume: 13
  start-page: 1116
  year: 2011
  end-page: 1123
  ident: CR65
  article-title: Endolysosomal sorting of ubiquitylated caveolin‐1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations
  publication-title: Nat Cell Biol
– volume: 527
  start-page: 389
  year: 2015
  end-page: 393
  ident: CR72
  article-title: Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage
  publication-title: Nature
– volume: 104
  start-page: 20759
  year: 2007
  end-page: 20763
  ident: CR76
  article-title: Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage
  publication-title: Proc Natl Acad Sci USA
– volume: 9
  start-page: 548
  year: 2013
  end-page: 556
  ident: CR45
  article-title: Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death
  publication-title: Nat Chem Biol
– volume: 64
  start-page: 704
  year: 2016
  end-page: 719
  ident: CR74
  article-title: Metalloprotease SPRTN/DVC1 orchestrates replication‐coupled DNA‐protein crosslink repair
  publication-title: Mol Cell
– volume: 72
  start-page: 4974
  year: 2012
  end-page: 4983
  ident: CR55
  article-title: RNF8 regulates assembly of RAD51 at DNA double‐strand breaks in the absence of BRCA1 and 53BP1
  publication-title: Can Res
– volume: 47
  start-page: 497
  year: 2012
  end-page: 510
  ident: CR15
  article-title: Playing the end game: DNA double‐strand break repair pathway choice
  publication-title: Mol Cell
– volume: 14
  start-page: 117
  year: 2012
  end-page: 123
  ident: CR52
  article-title: Emerging functions of the VCP/p97 AAA‐ATPase in the ubiquitin system
  publication-title: Nat Cell Biol
– volume: 14
  start-page: 661
  year: 2013
  end-page: 672
  ident: CR58
  article-title: Push back to respond better: regulatory inhibition of the DNA double‐strand break response
  publication-title: Nat Rev Mol Cell Biol
– volume: 15
  start-page: 526
  year: 2013
  end-page: 532
  ident: CR6
  article-title: Role of Cdc48/p97 as a SUMO‐targeted segregase curbing Rad51‐Rad52 interaction
  publication-title: Nat Cell Biol
– volume: 65
  start-page: 7533
  year: 2005
  end-page: 7540
  article-title: Valosin‐containing protein phosphorylation at Ser784 in response to DNA damage
  publication-title: Can Res
– volume: 174
  start-page: 963
  year: 2006
  end-page: 971
  article-title: Regulation of retrotranslocation by p97‐associated deubiquitinating enzyme ataxin‐3
  publication-title: J Cell Biol
– volume: 23
  start-page: 6469
  year: 2003
  end-page: 6483
  article-title: Ataxin‐3 interactions with rad23 and valosin‐containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin‐mediated proteolysis
  publication-title: Mol Cell Biol
– volume: 20
  start-page: 8602
  year: 2000
  end-page: 8612
  article-title: Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis
  publication-title: Mol Cell Biol
– volume: 73
  start-page: 1267
  year: 2019
  end-page: 1281
  article-title: BRCA1 haploinsufficiency is masked by RNF168‐mediated chromatin ubiquitylation
  publication-title: Mol Cell
– volume: 58
  start-page: 9480
  year: 2015
  end-page: 9497
  article-title: Discovery of a first‐in‐class, potent, selective, and orally bioavailable inhibitor of the p97 AAA ATPase (CB‐5083)
  publication-title: J Med Chem
– volume: 104
  start-page: 16910
  year: 2007
  end-page: 16915
  article-title: RIDDLE immunodeficiency syndrome is linked to defects in 53BP1‐mediated DNA damage signaling
  publication-title: Proc Natl Acad Sci USA
– volume: 101
  start-page: 7
  year: 2011
  end-page: 12
  article-title: The role of homologous recombination in radiation‐induced double‐strand break repair
  publication-title: Radiother Oncol
– volume: 64
  start-page: 189
  year: 2016
  end-page: 198
  article-title: VCP/p97 extracts sterically trapped Ku70/80 rings from DNA in Double‐strand break repair
  publication-title: Mol Cell
– volume: 64
  start-page: 51
  year: 2016
  end-page: 64
  article-title: 53BP1 integrates DNA repair and p53‐dependent cell fate decisions via distinct mechanisms
  publication-title: Mol Cell
– volume: 19
  start-page: 1
  year: 2016
  end-page: 9
  article-title: The control of DNA repair by the cell cycle
  publication-title: Nat Cell Biol
– volume: 127
  start-page: 3877
  year: 2014
  end-page: 3883
  article-title: The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis
  publication-title: J Cell Sci
– volume: 5
  start-page: 3695
  year: 2014
  article-title: Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity
  publication-title: Nat Commun
– volume: 288
  start-page: 2941
  year: 2013
  end-page: 2950
  article-title: Identification of RNF8 as a ubiquitin ligase involved in targeting the p12 subunit of DNA polymerase delta for degradation in response to DNA damage
  publication-title: J Biol Chem
– volume: 589
  start-page: 2578
  year: 2015
  end-page: 2589
  article-title: Control of p97 function by cofactor binding
  publication-title: FEBS Lett
– volume: 12
  start-page: 3195
  year: 2003
  end-page: 3205
  article-title: The polyglutamine neurodegenerative protein ataxin‐3 binds polyubiquitylated proteins and has ubiquitin protease activity
  publication-title: Hum Mol Genet
– volume: 150
  start-page: 697
  year: 2012
  end-page: 709
  article-title: TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes
  publication-title: Cell
– volume: 169
  start-page: 792
  year: 2017
  end-page: 806
  article-title: The logic of the 26S proteasome
  publication-title: Cell
– volume: 18
  start-page: 495
  year: 2017
  end-page: 506
  article-title: Non‐homologous DNA end joining and alternative pathways to double‐strand break repair
  publication-title: Nat Rev Mol Cell Biol
– volume: 35
  start-page: 88
  year: 2016
  article-title: RNF8 promotes epithelial‐mesenchymal transition of breast cancer cells
  publication-title: J Exp Clin Cancer Res
– volume: 108
  start-page: 4834
  year: 2011
  end-page: 4839
  article-title: Reversible inhibitor of p97, DBeQ, impairs both ubiquitin‐dependent and autophagic protein clearance pathways
  publication-title: Proc Natl Acad Sci USA
– volume: 104
  start-page: 20759
  year: 2007
  end-page: 20763
  article-title: Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage
  publication-title: Proc Natl Acad Sci USA
– volume: 47
  start-page: 497
  year: 2012
  end-page: 510
  article-title: Playing the end game: DNA double‐strand break repair pathway choice
  publication-title: Mol Cell
– volume: 162
  start-page: 71
  year: 2003
  end-page: 84
  article-title: Function of the p97‐Ufd1‐Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains
  publication-title: J Cell Biol
– volume: 15
  start-page: 526
  year: 2013
  end-page: 532
  article-title: Role of Cdc48/p97 as a SUMO‐targeted segregase curbing Rad51‐Rad52 interaction
  publication-title: Nat Cell Biol
– volume: 100
  start-page: 776
  year: 2018
  end-page: 784
  article-title: Complex DNA damage induced by high linear energy transfer alpha‐particles and protons triggers a specific cellular DNA damage response
  publication-title: Int J Radiat Oncol Biol Phys
– volume: 318
  start-page: 1637
  year: 2007
  end-page: 1640
  article-title: Orchestration of the DNA‐damage response by the RNF8 ubiquitin ligase
  publication-title: Science
– volume: 14
  start-page: 661
  year: 2013
  end-page: 672
  article-title: Push back to respond better: regulatory inhibition of the DNA double‐strand break response
  publication-title: Nat Rev Mol Cell Biol
– volume: 292
  start-page: 18392
  year: 2017
  end-page: 18407
  article-title: Interaction between the AAA(+) ATPase p97 and its cofactor ataxin3 in health and disease: nucleotide‐induced conformational changes regulate cofactor binding
  publication-title: J Biol Chem
– volume: 14
  start-page: 1413
  year: 2015
  end-page: 1425
  article-title: USP7 deubiquitinase promotes ubiquitin‐dependent DNA damage signaling by stabilizing RNF168
  publication-title: Cell Cycle
– volume: 212
  start-page: 465
  year: 2016
  end-page: 480
  article-title: Ataxin‐3 phosphorylation decreases neuronal defects in spinocerebellar ataxia type 3 models
  publication-title: J Cell Biol
– volume: 286
  start-page: 22355
  year: 2011
  end-page: 22361
  article-title: Critical roles of ring finger protein RNF8 in replication stress responses
  publication-title: J Biol Chem
– volume: 72
  start-page: 250
  year: 2018
  end-page: 262
  article-title: Comprehensive mapping of histone modifications at DNA double‐strand breaks deciphers repair pathway chromatin signatures
  publication-title: Mol Cell
– volume: 31
  start-page: 2511
  year: 2012
  end-page: 2527
  article-title: A new non‐catalytic role for ubiquitin ligase RNF8 in unfolding higher‐order chromatin structure
  publication-title: EMBO J
– volume: 461
  start-page: 1071
  year: 2009
  end-page: 1078
  article-title: The DNA‐damage response in human biology and disease
  publication-title: Nature
– volume: 471
  start-page: 1
  year: 2015
  end-page: 11
  article-title: How cancer cells hijack DNA double‐strand break repair pathways to gain genomic instability
  publication-title: Biochem J
– volume: 10
  start-page: 55
  year: 2009
  article-title: RNF168, a new RING finger, MIU‐containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX
  publication-title: BMC Mol Biol
– volume: 150
  start-page: 1182
  year: 2012
  end-page: 1195
  article-title: RNF168 ubiquitinates K13‐15 on H2A/H2AX to drive DNA damage signaling
  publication-title: Cell
– volume: 69
  start-page: 866
  year: 2018
  end-page: 878
  article-title: The ubiquitin E3/E4 ligase UBE4A adjusts protein ubiquitylation and accumulation at sites of DNA damage. Facilitating double‐strand break repair
  publication-title: Mol Cell
– volume: 16
  start-page: 35
  year: 2016
  end-page: 42
  article-title: DNA repair, genome stability and cancer: a historical perspective
  publication-title: Nat Rev Cancer
– volume: 14
  start-page: 117
  year: 2012
  end-page: 123
  article-title: Emerging functions of the VCP/p97 AAA‐ATPase in the ubiquitin system
  publication-title: Nat Cell Biol
– volume: 283
  start-page: 26436
  year: 2008
  end-page: 26443
  article-title: The deubiquitinating enzyme ataxin‐3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains
  publication-title: J Biol Chem
– volume: 61
  start-page: 449
  year: 2016
  end-page: 460
  article-title: Targeting BRCA1 and BRCA2 deficiencies with G‐quadruplex‐interacting compounds
  publication-title: Mol Cell
– volume: 64
  start-page: 704
  year: 2016
  end-page: 719
  article-title: Metalloprotease SPRTN/DVC1 orchestrates replication‐coupled DNA‐protein crosslink repair
  publication-title: Mol Cell
– volume: 5
  start-page: 986
  year: 2006
  end-page: 996
  article-title: DNA repair: from molecular mechanism to human disease
  publication-title: DNA Repair (Amst)
– volume: 63
  start-page: 1021
  year: 2016a
  end-page: 1033
  article-title: The DNA damage transducer RNF8 facilitates cancer chemoresistance and progression through twist activation
  publication-title: Mol Cell
– volume: 316
  start-page: 1198
  year: 2007
  end-page: 1202
  article-title: RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites
  publication-title: Science
– volume: 426
  start-page: 2886
  year: 2014
  end-page: 2899
  article-title: Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains
  publication-title: J Mol Biol
– volume: 3
  start-page: e1242454
  year: 2016b
  article-title: Two‐faced activity of RNF8: what “twists” it from a genome guardian to a cancer facilitator?
  publication-title: Mol Cell Oncol
– volume: 19
  start-page: 169
  year: 2014
  end-page: 175
  article-title: DNA double‐strand break repair pathway choice and cancer
  publication-title: DNA Repair (Amst)
– volume: 4
  start-page: e1000110
  year: 2008
  article-title: Alternative‐NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair
  publication-title: PLoS Genet
– volume: 7
  start-page: e43563
  year: 2012
  article-title: Valosin‐containing protein (VCP/p97) is an activator of wild‐type ataxin‐3
  publication-title: PLoS ONE
– volume: 136
  start-page: 435
  year: 2009
  end-page: 446
  article-title: RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins
  publication-title: Cell
– volume: 36
  start-page: 1066
  year: 2017
  end-page: 1083
  article-title: Ataxin‐3 consolidates the MDC1‐dependent DNA double‐strand break response by counteracting the SUMO‐targeted ubiquitin ligase RNF4
  publication-title: EMBO J
– volume: 40
  start-page: 196
  year: 2012
  end-page: 205
  article-title: Differential regulation of RNF8‐mediated Lys48‐ and Lys63‐based poly‐ubiquitylation
  publication-title: Nucleic Acids Res
– volume: 329
  start-page: 9
  year: 2014
  end-page: 17
  article-title: Should I stay or should I go: VCP/p97‐mediated chromatin extraction in the DNA damage response
  publication-title: Exp Cell Res
– volume: 31
  start-page: 1865
  year: 2012
  end-page: 1878
  article-title: RNF8‐ and RNF168‐dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites
  publication-title: EMBO J
– volume: 8
  start-page: 29963
  year: 2017
  end-page: 29975
  article-title: Misregulation of DNA damage repair pathways in HPV‐positive head and neck squamous cell carcinoma contributes to cellular radiosensitivity
  publication-title: Oncotarget
– volume: 13
  start-page: 1376
  year: 2011
  end-page: 1382
  article-title: The ubiquitin‐selective segregase VCP/p97 orchestrates the response to DNA double‐strand breaks
  publication-title: Nat Cell Biol
– volume: 131
  start-page: 887
  year: 2007
  end-page: 900
  article-title: RNF8 ubiquitylates histones at DNA double‐strand breaks and promotes assembly of repair proteins
  publication-title: Cell
– volume: 169
  start-page: 722
  year: 2017b
  end-page: 735
  article-title: Molecular mechanism of substrate processing by the Cdc48 ATPase complex
  publication-title: Cell
– volume: 136
  start-page: 420
  year: 2009
  end-page: 434
  article-title: The RIDDLE syndrome protein mediates a ubiquitin‐dependent signaling cascade at sites of DNA damage
  publication-title: Cell
– volume: 19
  start-page: 201
  year: 2012
  end-page: 206
  article-title: The E3 ligase RNF8 regulates KU80 removal and NHEJ repair
  publication-title: Nat Struct Mol Biol
– volume: 11
  start-page: 1062
  year: 2012
  end-page: 1069
  article-title: p97/VCP‐ and Lys48‐linked polyubiquitination form a new signaling pathway in DNA damage response
  publication-title: Cell Cycle
– volume: 20
  start-page: 1425
  year: 2013
  end-page: 1433
  article-title: JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1‐mediated chromatin response to DNA breaks
  publication-title: Nat Struct Mol Biol
– volume: 179
  start-page: 78
  year: 2012
  end-page: 82
  article-title: Expanding into new markets–VCP/p97 in endocytosis and autophagy
  publication-title: J Struct Biol
– volume: 18
  start-page: 1345
  year: 2011
  end-page: 1350
  article-title: The AAA‐ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double‐strand breaks
  publication-title: Nat Struct Mol Biol
– volume: 72
  start-page: 4974
  year: 2012
  end-page: 4983
  article-title: RNF8 regulates assembly of RAD51 at DNA double‐strand breaks in the absence of BRCA1 and 53BP1
  publication-title: Can Res
– volume: 527
  start-page: 389
  year: 2015
  end-page: 393
  article-title: Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage
  publication-title: Nature
– volume: 173
  start-page: 19
  year: 2006
  end-page: 26
  article-title: A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin remodeling
  publication-title: J Cell Biol
– volume: 287
  start-page: 40618
  year: 2012
  end-page: 40628
  article-title: RING finger nuclear factor RNF168 is important for defects in homologous recombination caused by loss of the breast cancer susceptibility factor BRCA1
  publication-title: J Biol Chem
– volume: 13
  start-page: 1116
  year: 2011
  end-page: 1123
  article-title: Endolysosomal sorting of ubiquitylated caveolin‐1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations
  publication-title: Nat Cell Biol
– volume: 20
  start-page: 954
  year: 2018
  end-page: 965
  article-title: Shieldin complex promotes DNA end‐joining and counters homologous recombination in BRCA1‐null cells
  publication-title: Nat Cell Biol
– volume: 316
  start-page: 1202
  year: 2007
  end-page: 1205
  article-title: Ubiquitin‐binding protein RAP80 mediates BRCA1‐dependent DNA damage response
  publication-title: Science
– volume: 66
  start-page: 458
  year: 2017
  end-page: 472
  article-title: RNF8‐ and Ube2S‐dependent ubiquitin lysine 11‐linkage modification in response to DNA damage
  publication-title: Mol Cell
– volume: 6
  start-page: 1318
  year: 2017a
  article-title: Toward an understanding of the Cdc48/p97 ATPase
  publication-title: F1000Res
– volume: 69
  start-page: 505
  year: 2018
  end-page: 516
  article-title: OTUD4 is a phospho‐activated K63 deubiquitinase that regulates MyD88‐dependent signaling
  publication-title: Mol Cell
– volume: 291
  start-page: 9396
  year: 2016
  end-page: 9410
  article-title: RNF8 E3 ubiquitin ligase stimulates Ubc13 E2 conjugating activity that is essential for DNA double strand break signaling and BRCA1 tumor suppressor recruitment
  publication-title: J Biol Chem
– volume: 27
  start-page: 3791
  year: 2016
  end-page: 3799
  article-title: The poly(ADP‐ribose)‐dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage
  publication-title: Mol Biol Cell
– volume: 291
  start-page: 1789
  year: 2016
  end-page: 1802
  article-title: Poly(ADP‐ribosyl)ation‐dependent transient chromatin decondensation and histone displacement following laser microirradiation
  publication-title: J Biol Chem
– volume: 4
  start-page: 60
  year: 2013
  article-title: Role of p97/VCP (Cdc48) in genome stability
  publication-title: Front Genet
– volume: 9
  start-page: 548
  year: 2013
  end-page: 556
  article-title: Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death
  publication-title: Nat Chem Biol
– volume: 15
  start-page: 2409
  year: 2006
  end-page: 2420
  article-title: Ataxin‐3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates
  publication-title: Hum Mol Genet
– volume: 23
  start-page: 995
  year: 2016
  end-page: 1002
  article-title: E4 ligase‐specific ubiquitination hubs coordinate DNA double‐strand‐break repair and apoptosis
  publication-title: Nat Struct Mol Biol
– volume: 10
  start-page: 226
  year: 2015
  end-page: 238
  article-title: RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage
  publication-title: Cell Rep
– volume: 560
  start-page: 117
  year: 2018
  end-page: 121
  article-title: The shieldin complex mediates 53BP1‐dependent DNA repair
  publication-title: Nature
SSID ssj0005871
Score 2.4969814
Snippet The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper‐accumulation is tumour‐promoting and positively...
The E3 ubiquitin ligase RNF8 (RING finger protein 8) is a pivotal enzyme for DNA repair. However, RNF8 hyper-accumulation is tumour-promoting and positively...
SourceID pubmedcentral
proquest
pubmed
wiley
springer
SourceType Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage e102361
SubjectTerms Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
Ataxin
Ataxin 3
Ataxin-3 - genetics
Ataxin-3 - metabolism
BRCA2 protein
Breast cancer
Cancer
Cell Survival
Chromatin
Chromatin - genetics
Damage
Deactivation
Deoxyribonucleic acid
DNA
DNA Breaks, Double-Stranded
DNA damage
DNA double‐strand break repair
DNA Repair
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
E3 ubiquitin ligase RNF8
EMBO13
EMBO31
genome stability
Genomes
Genomic Instability
Genotoxicity
HEK293 Cells
HeLa Cells
Homeostasis
Homologous recombination
Homology
Humans
Inactivation
Ionizing radiation
Medical prognosis
Metastases
Non-homologous end joining
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
p97/VCP ATPase
Physiology
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Proteolysis
Recruitment
Repair
Signal Transduction
Tumors
Ubiquitin
Ubiquitin - metabolism
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
Title The p97–Ataxin 3 complex regulates homeostasis of the DNA damage response E3 ubiquitin ligase RNF8
URI https://link.springer.com/article/10.15252/embj.2019102361
https://onlinelibrary.wiley.com/doi/abs/10.15252%2Fembj.2019102361
https://www.ncbi.nlm.nih.gov/pubmed/31613024
https://www.proquest.com/docview/2311474055
https://www.proquest.com/docview/2305799693
https://pubmed.ncbi.nlm.nih.gov/PMC6826192
Volume 38
WOSCitedRecordID wos000489982500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVWIB
  databaseName: Wiley Free Archive
  customDbUrl:
  eissn: 1460-2075
  dateEnd: 20231231
  omitProxy: false
  ssIdentifier: ssj0005871
  issn: 0261-4189
  databaseCode: WIN
  dateStart: 19970101
  isFulltext: true
  titleUrlDefault: https://onlinelibrary.wiley.com
  providerName: Wiley-Blackwell
– providerCode: PRVWIB
  databaseName: Wiley Online Library Full Collection 2020
  customDbUrl:
  eissn: 1460-2075
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0005871
  issn: 0261-4189
  databaseCode: DRFUL
  dateStart: 19970101
  isFulltext: true
  titleUrlDefault: https://onlinelibrary.wiley.com
  providerName: Wiley-Blackwell
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3NbtQwEB6hFkQv_BQogVIZiRNSRBInsX1c2l0BKhGqqNhbFMc2TdVNls0uam99B96QJ8Hj7GZZfi6ISyTLYyvJzNjfeMYzAC8UxxpIivm6ZMJHiO1LKyY-lTyMlUkN1S7P7DHLMj4ei5_vwnT5IfoDN9QMt16jgheyXVXswayheiLPMTZLYPYBtIC2w5ByLN8QxR_WYR7cGV3unCUOuVi6KnGOV7_M8CeQ-XusZO8w3YSzbj8a3f0fX3IP7izRKBl04nMfbuh6F2519SmvduH24aoc3ANQVqDIVLDv198G8-KyqgklLh5dX5JZV9Bet-SsmejGAs62akljiEWX5CgbEFVM7Lpl6VxAriZDShay-rKo5naei-qz3UrJSTbiD-F0NPx4-MZflmjwp-jg9BXHQniK01AZY9cDZtIiKGhstdokmjFhAqntDphYSVChSaIiLcskMFLbkZEo6SPYqptaPwZSBkJFQhYh1UHMaMllkmoTlIYKJaXhHuyvuJMv9azNLToNY2ZBZ-LB877b_hl0exS1bhZIgxduRSqoB3sdM_Npl8ojpyHaT1HsAdtgc0-A2bc3e-rqzGXhTrkzPj14uRKI9WuhZYW8zZGz-ZqzHiROEPrp_0aYD9-_frduPvnHcU9hBxsu-DDeh635bKGfwc3y67xqZwdOUeyTjfkBbB-djE6PbevT2-wHtK8WKw
linkProvider Wiley-Blackwell
linkToHtml http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lj9MwEB6tFtDuhcfyCixgJE5IEUmdxPaxlFa70I0QWsTeoji22aBtUpoWLTf-A_-QX4LHaVKVxwVxjDweJZkZ-xvPeAbgmeLYA0kxXxdM-AixfWnVxKeSh5EyiaHa1ZmdsjTlZ2fi7Q6MurswbX2I_sANLcOt12jgeCDdtezBsqF6Jj9hcpbA8gPoAl2JLN7A_g0fjtNNngd3Xpc7aIlCLtaxSuTx4hcOf0KZvydL9hHTbTzrNqTJjf_yKTfh-hqPkmGrQLdgR1cHcK3tUPn1APZGXUO426CsSpG5YD--fR8u88uyIpS4jHR9SRZtS3vdkPN6pmsLOZuyIbUhFl-SV-mQqHxmVy5L51JyNRlTspLl51W5tHwuyo92MyXv0gm_A-8n49PRkb9u0uDPMcTpK46t8BSnoTLGrgjMJHmQ08jatYk1Y8IEUts9MLa6oEITD_KkKOLASG1nDkRB78JuVVf6PpAiEGogZB5SHUSMFlzGiTZBYahQUhruwWEnnmxtaU1m8WkYMQs7Yw-e9sP2z2DgI690vUIavHIrEkE9uNdKM5u3xTwyGqIHNYg8YFty7gmw_vb2SFWeuzrcCXfupwfPO43YvBb6VijbDCWbbSTrQew0oWf_N8JsfPLy9ebxwT_OewJ7R6cn02x6nL55CPs44FIRo0PYXS5W-hFcLb4sy2bx2FnNTy_uFuw
linkToPdf http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lj9MwEB6tusBy4bGwEFjASJyQIpI6D_tY2kY8SrRasdLeoji22SCalD7QcuM_8A_5JXicR1UeF8QxyXiUZGbsbzzjGYBnkmEPJBm7qoi5ixDbFUZNXCqYH0gdaapsndlZnKbs_Jyf7MG4OwvT1IfoN9zQMux8jQauFlJ3LXuwbKiai4-YnMWx_AC6QPsB9pIZwP7kNDmbbTM9mPW77FZL4DPeRiuRy4tfePwJZ_6eLtnHTHcRrV2Skpv_5WNuwY0WkZJRo0K3YU9Vh3C16VH59RAOxl1LuDsgjVKRBY9_fPs-WueXZUUosTnp6pIsm6b2akUu6rmqDehclStSa2IQJpmkIyLzuZm7DJ1NylVkSslGlJ835drw-VR-MMspOU0TdhfOkun78Su3bdPgLjDI6UqGzfAko77U2swJsY5yL6eBsWwdqjjm2hPKrIKh0Qbp63CYR0URelooM3LIC3oEg6qu1H0ghcflkIvcp8oLYlowEUZKe4WmXAqhmQPHnXiy1tZWmUGofhAb4Bk68LR_bP4Mhj7yStUbpMFDtzzi1IF7jTSzRVPOI6M--lDDwIF4R849AVbg3n1SlRe2EnfErAPqwPNOI7avhd4VyjZDyWZbyToQWk3o2f-NMJu-e_lme_ngH8c9gWsnkySbvU7fPoTreN_mIgbHMFgvN-oRXCm-rMvV8nFrNj8BCL8XlQ
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+p97-Ataxin+3+complex+regulates+homeostasis+of+the+DNA+damage+response+E3+ubiquitin+ligase+RNF8&rft.jtitle=The+EMBO+journal&rft.au=Singh%2C+Abhay+Narayan&rft.au=Oehler%2C+Judith&rft.au=Torrecilla%2C+Ignacio&rft.au=Kilgas%2C+Susan&rft.date=2019-10-04&rft.issn=1460-2075&rft.eissn=1460-2075&rft.volume=38&rft.issue=21&rft.spage=e102361&rft_id=info:doi/10.15252%2Fembj.2019102361&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0261-4189&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0261-4189&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0261-4189&client=summon