Molecular dependencies and genomic consequences of a global DNA damage tolerance defect
DNA damage tolerance (DDT) enables replication to continue in the presence of fork stalling lesions. To determine the molecular and genomic impact of a global DDT defect, we studied PcnaK164R/-;Rev1-/- compound mutants. Double mutant (DM) cells displayed increased replication stress, hypersensitivit...
Uloženo v:
| Vydáno v: | bioRxiv |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , |
| Médium: | Paper |
| Jazyk: | angličtina |
| Vydáno: |
Cold Spring Harbor
Cold Spring Harbor Laboratory Press
06.11.2023
Cold Spring Harbor Laboratory |
| Vydání: | 1.2 |
| Témata: | |
| ISSN: | 2692-8205, 2692-8205 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | DNA damage tolerance (DDT) enables replication to continue in the presence of fork stalling lesions. To determine the molecular and genomic impact of a global DDT defect, we studied PcnaK164R/-;Rev1-/- compound mutants. Double mutant (DM) cells displayed increased replication stress, hypersensitivity to genotoxic agents, replication speed, and repriming. A whole genome CRISPR-Cas9 screen revealed a strict reliance of DM cells on the CST complex, where CST promotes fork stability. Whole genome sequencing indicated that this DM DDT defect favors the generation of large, replication-stress inducible deletions of 0.4-4.0kbp, defined as type 3 deletions. Junction break sites of these deletions revealed preferential microhomology preferences of 1-2 base pairs, differing from the smaller type 1 and type 2 deletions. These differential characteristics suggest the existence of molecularly distinct deletion pathways. Type 3 deletions are abundant in human tumors, can dominate the deletion landscape and are associated with DNA damage response status and treatment modality. Our data highlight the essential contribution of the DDT system to genome maintenance and type 3 deletions as mutational signature of replication stress. The unique characteristics of type 3 deletions implicate the existence of a novel deletion pathway in mice and humans that is counteracted by DDT.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Corrected some typographical errors and improved layout. |
|---|---|
| AbstractList | DNA damage tolerance (DDT) enables replication to continue in the presence of fork stalling lesions. To determine the molecular and genomic impact of a global DDT defect, we studied PcnaK164R/-;Rev1-/- compound mutants. Double mutant (DM) cells displayed increased replication stress, hypersensitivity to genotoxic agents, replication speed, and repriming. A whole genome CRISPR-Cas9 screen revealed a strict reliance of DM cells on the CST complex, where CST promotes fork stability. Whole genome sequencing indicated that this DM DDT defect favors the generation of large, replication-stress inducible deletions of 0.4-4.0kbp, defined as type 3 deletions. Junction break sites of these deletions revealed preferential microhomology preferences of 1-2 base pairs, differing from the smaller type 1 and type 2 deletions. These differential characteristics suggest the existence of molecularly distinct deletion pathways. Type 3 deletions are abundant in human tumors, can dominate the deletion landscape and are associated with DNA damage response status and treatment modality. Our data highlight the essential contribution of the DDT system to genome maintenance and type 3 deletions as mutational signature of replication stress. The unique characteristics of type 3 deletions implicate the existence of a novel deletion pathway in mice and humans that is counteracted by DDT. DNA damage tolerance (DDT) enables replication to continue in the presence of fork stalling lesions. To determine the molecular and genomic impact of a global DDT defect, we studied PcnaK164R/-;Rev1-/- compound mutants. Double mutant (DM) cells displayed increased replication stress, hypersensitivity to genotoxic agents, replication speed, and repriming. A whole genome CRISPR-Cas9 screen revealed a strict reliance of DM cells on the CST complex, where CST promotes fork stability. Whole genome sequencing indicated that this DM DDT defect favors the generation of large, replication-stress inducible deletions of 0.4-4.0kbp, defined as type 3 deletions. Junction break sites of these deletions revealed preferential microhomology preferences of 1-2 base pairs, differing from the smaller type 1 and type 2 deletions. These differential characteristics suggest the existence of molecularly distinct deletion pathways. Type 3 deletions are abundant in human tumors, can dominate the deletion landscape and are associated with DNA damage response status and treatment modality. Our data highlight the essential contribution of the DDT system to genome maintenance and type 3 deletions as mutational signature of replication stress. The unique characteristics of type 3 deletions implicate the existence of a novel deletion pathway in mice and humans that is counteracted by DDT.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Corrected some typographical errors and improved layout. |
| Author | Shah, Ronak Morris, Ben Buoninfante, Olimpia Alessandra Cor Lieftink Sr Joyce Ji Catsman Pilzecker, Bas Kreft, Maaike Paul Cm Van Denberk Jacobs, Heinz Spanjaard, Aldo Ormel, Shirley Ayidah, Matilda Beijersbergen, Roderick L Groot, Daniel De |
| Author_xml | – sequence: 1 givenname: Daniel surname: Groot middlename: De fullname: Groot, Daniel De – sequence: 2 givenname: Aldo surname: Spanjaard fullname: Spanjaard, Aldo – sequence: 3 givenname: Ronak surname: Shah fullname: Shah, Ronak – sequence: 4 givenname: Maaike surname: Kreft fullname: Kreft, Maaike – sequence: 5 givenname: Ben surname: Morris fullname: Morris, Ben – sequence: 6 fullname: Cor Lieftink Sr – sequence: 7 fullname: Joyce Ji Catsman – sequence: 8 givenname: Shirley surname: Ormel fullname: Ormel, Shirley – sequence: 9 givenname: Matilda surname: Ayidah fullname: Ayidah, Matilda – sequence: 10 givenname: Bas surname: Pilzecker fullname: Pilzecker, Bas – sequence: 11 givenname: Olimpia surname: Buoninfante middlename: Alessandra fullname: Buoninfante, Olimpia Alessandra – sequence: 12 fullname: Paul Cm Van Denberk – sequence: 13 givenname: Roderick surname: Beijersbergen middlename: L fullname: Beijersbergen, Roderick L – sequence: 14 givenname: Heinz surname: Jacobs fullname: Jacobs, Heinz |
| BookMark | eNpNkDtPAzEQhC0UJELID6CzRENzwfbZZ18ZhacUoAFRWn6so4sudvAlCP49hlBQ7a7m02hnTtEopggInVMyo5TQK0ZYPfs9ZqKhSvAjNGZNyyrFiBj920_QdBjWhBDWNrSWfIzeHlMPbt-bjD1sIXqIroMBm-jxCmLadA67FAd43xelCClgg1d9sqbH109z7M3GrADvik02hSg2AdzuDB0H0w8w_ZsT9Hp787K4r5bPdw-L-bKylHBeWQjB2GCk58Bq2YK0gQtqWiUk1B4oB-Fq6RtPPWtsYII55hQLMrTCK1ZP0OXB13Ypf3Yfepu7jclf-qcTTYmmVB86KejFAd3mVNIMO71O-xzLd5op1XAhBFf1N5RzYwU |
| ContentType | Paper |
| Copyright | 2023. Notwithstanding the ProQuest Terms and conditions, you may use this content in accordance with the associated terms available at https://www.biorxiv.org/content/10.1101/2023.10.11.561854v2 2023, Posted by Cold Spring Harbor Laboratory |
| Copyright_xml | – notice: 2023. Notwithstanding the ProQuest Terms and conditions, you may use this content in accordance with the associated terms available at https://www.biorxiv.org/content/10.1101/2023.10.11.561854v2 – notice: 2023, Posted by Cold Spring Harbor Laboratory |
| DBID | FX. |
| DOI | 10.1101/2023.10.11.561854 |
| DatabaseName | bioRxiv |
| DatabaseTitleList | |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 2692-8205 |
| Edition | 1.2 |
| ExternalDocumentID | 2023.10.11.561854v2 |
| Genre | Working Paper/Pre-Print |
| GroupedDBID | 8FE 8FH AFKRA ALMA_UNASSIGNED_HOLDINGS BBNVY BENPR BHPHI CCPQU HCIFZ LK8 M7P NQS PHGZM PHGZT PIMPY PQGLB PROAC RHI FX. |
| ID | FETCH-LOGICAL-b1044-beffabfa7d4e2379e7bf451a9857e3de14e5c37d6d1d26bf252c2c82f7f95d823 |
| ISSN | 2692-8205 |
| IngestDate | Tue Jan 07 18:59:30 EST 2025 Fri Jul 25 09:19:00 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | false |
| IsScholarly | false |
| Language | English |
| License | The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission. |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-b1044-beffabfa7d4e2379e7bf451a9857e3de14e5c37d6d1d26bf252c2c82f7f95d823 |
| Notes | SourceType-Working Papers-1 ObjectType-Working Paper/Pre-Print-1 content type line 50 Competing Interest Statement: The authors have declared no competing interest. |
| OpenAccessLink | https://www.biorxiv.org/content/10.1101/2023.10.11.561854 |
| PQID | 2886455548 |
| PQPubID | 2050091 |
| PageCount | 39 |
| ParticipantIDs | biorxiv_primary_2023_10_11_561854 proquest_journals_2886455548 |
| PublicationCentury | 2000 |
| PublicationDate | 20231106 |
| PublicationDateYYYYMMDD | 2023-11-06 |
| PublicationDate_xml | – month: 11 year: 2023 text: 20231106 day: 06 |
| PublicationDecade | 2020 |
| PublicationPlace | Cold Spring Harbor |
| PublicationPlace_xml | – name: Cold Spring Harbor |
| PublicationTitle | bioRxiv |
| PublicationYear | 2023 |
| Publisher | Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory |
| Publisher_xml | – name: Cold Spring Harbor Laboratory Press – name: Cold Spring Harbor Laboratory |
| References | van Bostelen, van Schendel, Romeijn, Tijsterman (2023.10.11.561854v2.78) 2020; 16 Friedberg (2023.10.11.561854v2.9) 2005; 6 Barazas, Annunziato, Pevf, de Krijger, Ghezraoui, Roobol, Lutz, Frankum, Song, Brough (2023.10.11.561854v2.40) 2018; 23 Zhang, Wang, Li, Liu, Xiao, Geng, Li, Liu, Price, Liu (2023.10.11.561854v2.58) 2019; 47 Edmunds, Simpson, Sale (2023.10.11.561854v2.24) 2008; 30 Langerak, Nygren, Krijger, van den Berk, Jacobs (2023.10.11.561854v2.37) 2007; 204 Ogi, Limsirichaikul, Overmeer, Volker, Takenaka, Cloney, Nakazawa, Niimi, Miki, Jaspers (2023.10.11.561854v2.17) 2010; 37 Hara, Nakaoka, Miyoshi, Ishikawa (2023.10.11.561854v2.43) 2023; 18 Chang, Pannunzio, Adachi, Lieber (2023.10.11.561854v2.11) 2017; 18 Buoninfante, Pilzecker, Aslam, Zavrakidis, van der Wiel, van de Ven, van den Berk, Jacobs (2023.10.11.561854v2.46) 2018; 9 Chou (2023.10.11.561854v2.49) 2010; 70 Gasparayan, Caridi, Julius, Feng, Bachant, Nugent (2023.10.11.561854v2.44) 2022; 68 Marsn-Pardillos, Tsaalbi-Shtylik, Chen, Lazare, van Os, Dethmers-Ausema, Fakouri, Bosshard, Aprigliano, van Loon (2023.10.11.561854v2.33) 2017; 130 Pilzecker, Jacobs (2023.10.11.561854v2.57) 2019; 10 Hendel, Krijger, Diamant, Goren, Langerak, Kim, Reißner, Lee, Geacintov, Carell (2023.10.11.561854v2.70) 2011; 7 Budzowska, Graham, Sobeck, Waga, Walter (2023.10.11.561854v2.16) 2015; 34 Garaycoechea, Crossan, Langevin, Mulderrig, Louzada, Yang, Guilbaud, Park, Roerink, Nik-Zainal (2023.10.11.561854v2.2) 2018; 553 Wit, Buoninfante, van den Berk, Jansen, Hogenbirk, de Wind, Jacobs (2023.10.11.561854v2.21) 2015; 43 Alexandrov, Kim, Haradhvala, Huang, Tian Ng, Wu, Boot, Covington, Gordenin, Bergstrom (2023.10.11.561854v2.63) 2020; 578 Spanjaard, Shah, de Groot, Buoninfante, Morris, Lietink, Pritchard, Zürcher, Ormel, Catsman (2023.10.11.561854v2.36) 2022; 50 Pilzecker, Buoninfante, Van Den Berk, Lancini, Song, Ciferio, Jacobs (2023.10.11.561854v2.7) 2017; 114 Dirac, Bernards (2023.10.11.561854v2.47) 2003; 278 Li, Durbin (2023.10.11.561854v2.50) 2009; 25 Cameron, Schröder, Penington, Do, Molania, Dobrovic, Speed, Papenfuss (2023.10.11.561854v2.51) 2017; 27 Quinet, Carvajal-Maldonado, Lemacon, Vindigni (2023.10.11.561854v2.56) 2017 Wu, Yang, Tsai (2023.10.11.561854v2.13) 2017; 1 Guo, Fischhaber, Luk-Paszyc, Masuda, Zhou, Kamiya, Kisker, Friedberg (2023.10.11.561854v2.26) 2003; 22 Sharma, Canman (2023.10.11.561854v2.76) 2012; 53 Gao, Mufer-Rofmayer, Greenwalt, Goldfarb, Yan, Yang, Martinez-Chacin, Pearce, Tateishi, Major (2023.10.11.561854v2.10) 2016; 7 Daigaku, Davies, Ulrich (2023.10.11.561854v2.22) 2010; 465 Vujanovic, Krietsch, Raso, Terraneo, Zellweger, Schmid, Taglialatela, Huang, Holland, Zwicky (2023.10.11.561854v2.23) 2017; 67 Schumacher, Pothof, Vijg, Hoeijmakers (2023.10.11.561854v2.3) 2021; 592 Maya-Mendoza, Moudry, Merchut-Maya, Lee, Strauss, Bartek (2023.10.11.561854v2.74) 2018; 559 Lyu, Lei, Biak Sang, Shiva, Chastain, Chi, Chai (2023.10.11.561854v2.41) 2021; 40 Bainbridge, Teague, Doherty (2023.10.11.561854v2.67) 2021; 49 Klug, Cummings, Spencer, Palladino (2023.10.11.561854v2.60) 2015 Yang, Gao (2023.10.11.561854v2.29) 2018; 87 He, Lin, Chavez, Agrawal, Lusk, Lim (2023.10.11.561854v2.45) 2022; 608 Tsuda, Terada, Ooka, Kobayashi, Sasanuma, Fujisawa, Tsurimoto, Yamamoto, Iwai, Kadoda (2023.10.11.561854v2.54) 2017; 8 Hodskinson, Bolner, Sato, Kamimae-Lanning, Rooijers, Wife, Mahesh, Silhan, Petek, Williams (2023.10.11.561854v2.32) 2020; 579 Tubbs, Nussenzweig (2023.10.11.561854v2.1) 2017; 168 Avkin, Sevilya, Toube, Geacintov, Chaney, Oren, Livneh (2023.10.11.561854v2.34) 2006; 22 Koole, Van Schendel, Karambelas, Van Heteren, Okihara, Tijsterman (2023.10.11.561854v2.73) 2014; 5 Pilzecker, Buoninfante, Pritchard, Blomberg, Huijbers, van den Berk, Jacobs (2023.10.11.561854v2.14) 2016; 44 Murga, Campaner, Lopez-Contreras, Toledo, Soria, Montaña, D’Artista, Schleker, Guerra, Garcia (2023.10.11.561854v2.71) 2011; 18 Quinet, Tirman, Cybulla, Meroni, Vindigni (2023.10.11.561854v2.68) 2021; 81 Knipscheer, Enoiu, Angelov, Sun, Griffith, Walter, Ellenberger, Scha (2023.10.11.561854v2.15) 2008; 134 Ross, Simpson, Sale (2023.10.11.561854v2.25) 2005; 33 Goodman, Woodgate (2023.10.11.561854v2.30) 2013; 5 Roepman, de Bruijn, van Lieshout, Schoenmaker, Boelens, Dubbink, Geurts-Giele, Groenendijk, Huibers, Kranendonk (2023.10.11.561854v2.53) 2021; 23 Scully, Panday, Elango, Willis (2023.10.11.561854v2.61) 2019; 20 Ran, Hsu, Wright, Agarwala, Scof, Zhang (2023.10.11.561854v2.48) 2013; 8 Stewart, Wang, Ackerson, Schuck (2023.10.11.561854v2.59) 2018; 23 Gyüre, Póti, Németh, Szikriszt, Lózsa, Krawczyk, Richardson, Szüts (2023.10.11.561854v2.79) 2023; 42 Nguyen, Kim, Le, Ding, Jaiswal, Kostlan, Nguyen, Shiva, Le, Chai (2023.10.11.561854v2.42) 2023; 9 Rossi, Bryder, Seita, Nussenzweig, Hoeijmakers, Weissman (2023.10.11.561854v2.4) 2007; 447 Chapman, Taylor, Boulton (2023.10.11.561854v2.62) 2012; 47 Deans, West (2023.10.11.561854v2.77) 2011; 11 Wu, Semlow, Kamimae-Lanning, Kochenova, Chistol, Hodskinson, Amunugama, Sparks, Wang, Deng (2023.10.11.561854v2.6) 2019; 567 Quinet, Martins, Vessoni, Biard, Sarasin, Stary, Menck (2023.10.11.561854v2.27) 2016; 44 Weaver, Click, Khoang, Todd Washington, Agarwal, Freudenthal (2023.10.11.561854v2.31) 2022; 13 Tzelepis, Koike-Yusa, De Braekeleer, Li, Metzakopian, Dovey, Mupo, Grinkevich, Li, Mazan (2023.10.11.561854v2.55) 2016; 17 Lopes, Foiani, Sogo (2023.10.11.561854v2.75) 2006; 21 Parra, Windle (2023.10.11.561854v2.65) 1993; 5 Jacobs, Doerdelmann, Krietsch, González-Acosta, Mathis, Kushinsky, Guarino, Gómez-Escolar, Martinez, Schmid (2023.10.11.561854v2.66) 2022; 82 Biertümpfel, Zhao, Kondo, Ramón-Maiques, Gregory, Lee, Masutani, Lehmann, Hanaoka, Yang (2023.10.11.561854v2.5) 2010; 465 Mcculloch, Kunkel (2023.10.11.561854v2.12) 2008; 18 Rice, Skordalakes (2023.10.11.561854v2.39) 2016; 14 Mailand, Gibbs-Seymour, Bekker-Jensen (2023.10.11.561854v2.28) 2013; 14 Tomas-Roca, Tsaalbi-Shtylik, Jansen, Singh, Epstein, Altunoglu, Verzijl, Soria, van Beusekom, Roscioli (2023.10.11.561854v2.8) 2015; 6 McCulloch, Kunkel (2023.10.11.561854v2.20) 2008; 18 Silverstein, Johnson, Jain, Prakash, Prakash, Aggarwal (2023.10.11.561854v2.35) 2010; 465 Bensimon, Simon, Chiffaudel, Croquefe, Heslot, Bensimon (2023.10.11.561854v2.64) 1994; 265 Krijger, van den Berk, Wit, Langerak, Jansen, Reynaud, de Wind, Jacobs (2023.10.11.561854v2.69) 2011; 10 Sale, Lehmann, Woodgate (2023.10.11.561854v2.19) 2012; 13 Gaillard, García-Muse, Aguilera (2023.10.11.561854v2.72) 2015; 15 Auwera (2023.10.11.561854v2.52) 2020 Pilzecker, Buoninfante, Jacobs (2023.10.11.561854v2.18) 2019; 47 Buoninfante, Pilzecker, Spanjaard, de Groot, Prekovic, Song, Lietink, Ayidah, Pritchard, Vivié (2023.10.11.561854v2.38) 2023; 120 |
| References_xml | – volume: 18 start-page: e0289304 year: 2023 ident: 2023.10.11.561854v2.43 article-title: The CST complex facilitates cell survival under oxidative genotoxic stress publication-title: PloS One – volume: 68 start-page: 165 year: 2022 end-page: 179 ident: 2023.10.11.561854v2.44 article-title: Yeast Stn1 promotes MCM to circumvent Rad53 control of the S phase checkpoint publication-title: Curr. Genet – volume: 20 start-page: 698 year: 2019 end-page: 714 ident: 2023.10.11.561854v2.61 article-title: DNA double-strand break repair-pathway choice in somatic mammalian cells publication-title: Nat. Rev. Mol. Cell Biol – volume: 204 start-page: 1989 year: 2007 end-page: 1998 ident: 2023.10.11.561854v2.37 article-title: A/T mutagenesis in hypermutated immunoglobulin genes strongly depends on PCNAK164 modification publication-title: J. Exp. Med – volume: 16 start-page: 1 year: 2020 end-page: 20 ident: 2023.10.11.561854v2.78 article-title: Translesion synthesis polymerases are dispensable for C. Elegans reproduction but suppress genome scarring by polymerase theta-mediated end joining publication-title: PLoS Genet – volume: 592 start-page: 695 year: 2021 end-page: 703 ident: 2023.10.11.561854v2.3 article-title: The central role of DNA damage in the ageing process publication-title: Nature – volume: 7 start-page: 12105 year: 2016 ident: 2023.10.11.561854v2.10 article-title: A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis publication-title: Nat. Commun – volume: 7 start-page: e1002262 year: 2011 ident: 2023.10.11.561854v2.70 article-title: PCNA Ubiquitination Is Important, But Not Essential for Translesion DNA Synthesis in Mammalian Cells publication-title: PLOS Genet – volume: 15 start-page: 276 year: 2015 end-page: 289 ident: 2023.10.11.561854v2.72 article-title: Replication stress and cancer publication-title: Nat. Rev. Cancer – volume: 44 start-page: 5717 year: 2016 end-page: 5731 ident: 2023.10.11.561854v2.27 article-title: Translesion synthesis mechanisms depend on the nature of DNA damage in UV-irradiated human cells publication-title: Nucleic Acids Res – volume: 9 start-page: eadd8023 year: 2023 ident: 2023.10.11.561854v2.42 article-title: Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair publication-title: Sci. Adv – volume: 18 start-page: 1331 year: 2011 end-page: 1335 ident: 2023.10.11.561854v2.71 article-title: Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors publication-title: Nat. Struct. Mol. Biol – volume: 579 start-page: 603 year: 2020 end-page: 608 ident: 2023.10.11.561854v2.32 article-title: Alcohol-derived DNA crosslinks are repaired by two distinct mechanisms publication-title: Nature – volume: 130 start-page: 1523 year: 2017 end-page: 1534 ident: 2023.10.11.561854v2.33 article-title: Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions publication-title: Blood – volume: 34 start-page: 1971 year: 2015 end-page: 1985 ident: 2023.10.11.561854v2.16 article-title: Regulation of the Rev1–pol ζ complex during bypass of a DNA interstrand cross-link publication-title: EMBO J – volume: 70 start-page: 440 year: 2010 end-page: 446 ident: 2023.10.11.561854v2.49 article-title: Drug combination studies and their synergy quantification using the Chou-Talalay method publication-title: Cancer Res – volume: 465 start-page: 1039 year: 2010 end-page: 1043 ident: 2023.10.11.561854v2.35 article-title: Structural basis for the suppression of skin cancers by DNA polymerase η publication-title: Nature – volume: 567 start-page: 267 year: 2019 end-page: 272 ident: 2023.10.11.561854v2.6 article-title: TRAIP is a master regulator of DNA interstrand crosslink repair publication-title: Nature – volume: 8 start-page: 33457 year: 2017 end-page: 33474 ident: 2023.10.11.561854v2.54 article-title: The dominant role of proofreading exonuclease activity of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C) publication-title: Oncotarget – year: 2017 ident: 2023.10.11.561854v2.56 article-title: DNA Fiber Analysis: Mind the Gap! 1st ed publication-title: Elsevier Inc – volume: 13 start-page: 2876 year: 2022 ident: 2023.10.11.561854v2.31 article-title: Mechanism of nucleotide discrimination by the translesion synthesis polymerase Rev1 publication-title: Nat. Commun – volume: 465 start-page: 951 year: 2010 end-page: 955 ident: 2023.10.11.561854v2.22 article-title: Ubiquitin-dependent DNA damage bypass is separable from genome replication publication-title: Nature – volume: 8 start-page: 2281 year: 2013 end-page: 2308 ident: 2023.10.11.561854v2.48 article-title: Genome engineering using the CRISPR-Cas9 system publication-title: Nat. Protoc – volume: 17 start-page: 1193 year: 2016 end-page: 1205 ident: 2023.10.11.561854v2.55 article-title: A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia publication-title: Cell Rep – volume: 10 start-page: 1051 year: 2011 end-page: 1059 ident: 2023.10.11.561854v2.69 article-title: PCNA ubiquitination-independent activation of polymerase η during somatic hypermutation and DNA damage tolerance publication-title: DNA Repair – volume: 11 start-page: 467 year: 2011 end-page: 480 ident: 2023.10.11.561854v2.77 article-title: DNA interstrand crosslink repair and cancer publication-title: Nat. Rev. Cancer – volume: 81 start-page: 649 year: 2021 end-page: 658 ident: 2023.10.11.561854v2.68 article-title: To skip or not to skip: choosing repriming to tolerate DNA damage publication-title: Mol. Cell – volume: 465 start-page: 1044 year: 2010 end-page: 1048 ident: 2023.10.11.561854v2.5 article-title: Structure and mechanism of human DNA polymerase eta publication-title: Nature – volume: 22 start-page: 407 year: 2006 end-page: 413 ident: 2023.10.11.561854v2.34 article-title: p53 and p21 Regulate Error-Prone DNA Repair to Yield a Lower Mutation Load publication-title: Mol. Cell – volume: 23 start-page: 1564 year: 2018 end-page: 1586 ident: 2023.10.11.561854v2.59 article-title: Emerging roles of CST in maintaining genome stability and human disease publication-title: Front. Biosci. Landmark Ed – volume: 23 start-page: 816 year: 2021 end-page: 833 ident: 2023.10.11.561854v2.53 article-title: Clinical Validation of Whole Genome Sequencing for Cancer Diagnostics publication-title: J. Mol. Diagn. JMD – volume: 14 start-page: 161 year: 2016 end-page: 167 ident: 2023.10.11.561854v2.39 article-title: Structure and function of the telomeric CST complex publication-title: Comput. Struct. Biotechnol. J – volume: 13 start-page: 141 year: 2012 end-page: 152 ident: 2023.10.11.561854v2.19 article-title: Y-family DNA polymerases and their role in tolerance of cellular DNA damage publication-title: Nat. Rev. Mol. Cell Biol – volume: 18 start-page: 148 year: 2008 end-page: 161 ident: 2023.10.11.561854v2.20 article-title: The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases publication-title: Cell Res – volume: 40 start-page: e103654 year: 2021 ident: 2023.10.11.561854v2.41 article-title: Human CST complex protects stalled replication forks by directly blocking MRE11 degradation of nascent-strand DNA publication-title: EMBO J – volume: 27 start-page: 2050 year: 2017 end-page: 2060 ident: 2023.10.11.561854v2.51 article-title: GRIDSS: sensitive and specific genomic rearrangement detection using positional de Bruijn graph assembly publication-title: Genome Res – volume: 120 start-page: e2216055120 year: 2023 ident: 2023.10.11.561854v2.38 article-title: Mammalian life depends on two distinct pathways of DNA damage tolerance publication-title: Proc. Natl. Acad. Sci. U. S. A – volume: 23 start-page: 2107 year: 2018 end-page: 2118 ident: 2023.10.11.561854v2.40 article-title: The CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells publication-title: Cell Rep – volume: 278 start-page: 11731 year: 2003 end-page: 11734 ident: 2023.10.11.561854v2.47 article-title: Reversal of senescence in mouse fibroblasts through lentiviral suppression of p53 publication-title: J. Biol. Chem – volume: 5 start-page: 1 year: 2014 end-page: 10 ident: 2023.10.11.561854v2.73 article-title: A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites publication-title: Nat. Commun – volume: 608 start-page: 826 year: 2022 end-page: 832 ident: 2023.10.11.561854v2.45 article-title: Structures of the human CST-Polα– primase complex bound to telomere templates publication-title: Nature – volume: 53 start-page: 725 year: 2012 end-page: 740 ident: 2023.10.11.561854v2.76 article-title: REV1 and DNA polymerase zeta in DNA interstrand crosslink repair publication-title: Environ. Mol. Mutagen – volume: 47 start-page: 7163 year: 2019 end-page: 7181 ident: 2023.10.11.561854v2.18 article-title: DNA damage tolerance in stem cells, ageing, mutagenesis, disease and cancer therapy publication-title: Nucleic Acids Res – volume: 553 start-page: 171 year: 2018 end-page: 177 ident: 2023.10.11.561854v2.2 article-title: Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells publication-title: Nature – volume: 134 start-page: 969 year: 2008 end-page: 980 ident: 2023.10.11.561854v2.15 article-title: Mechanism of Replication-Coupled DNA Interstrand Crosslink Repair publication-title: Cell – year: 2020 ident: 2023.10.11.561854v2.52 publication-title: Genomics in the cloud Using docker, gatk, and wdl in terra – volume: 82 start-page: 4176 year: 2022 end-page: 4188 ident: 2023.10.11.561854v2.66 article-title: Stress-triggered hematopoietic stem cell proliferation relies on PrimPol-mediated repriming publication-title: Mol. Cell – volume: 18 start-page: 495 year: 2017 end-page: 506 ident: 2023.10.11.561854v2.11 article-title: Non-homologous DNA end joining and alternative pathways to double-strand break repair publication-title: Nat. Rev. Mol. Cell Biol – volume: 6 start-page: 7199 year: 2015 ident: 2023.10.11.561854v2.8 article-title: De novo mutations in PLXND1 and REV3L cause Möbius syndrome publication-title: Nat. Commun – volume: 6 start-page: 943 year: 2005 end-page: 953 ident: 2023.10.11.561854v2.9 article-title: Suffering in silence: the tolerance of DNA damage publication-title: Nat. Rev. Mol. Cell Biol – volume: 18 start-page: 148 year: 2008 end-page: 161 ident: 2023.10.11.561854v2.12 article-title: The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases publication-title: Cell Res – volume: 5 start-page: a010363 year: 2013 ident: 2023.10.11.561854v2.30 article-title: Translesion DNA polymerases publication-title: Cold Spring Harb. Perspect. Biol – volume: 44 start-page: 4734 year: 2016 end-page: 4744 ident: 2023.10.11.561854v2.14 article-title: PrimPol prevents APOBEC/AID family mediated DNA mutagenesis publication-title: Nucleic Acids Res – volume: 578 start-page: 94 year: 2020 end-page: 101 ident: 2023.10.11.561854v2.63 article-title: The repertoire of mutational signatures in human cancer publication-title: Nature – volume: 67 start-page: 882 year: 2017 end-page: 890 ident: 2023.10.11.561854v2.23 article-title: Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity publication-title: Mol. Cell – volume: 25 start-page: 1754 year: 2009 end-page: 1760 ident: 2023.10.11.561854v2.50 article-title: Fast and accurate short read alignment with Burrows-Wheeler transform publication-title: Bioinforma. Oxf. Engl – volume: 37 start-page: 714 year: 2010 end-page: 727 ident: 2023.10.11.561854v2.17 article-title: Three DNA Polymerases, Recruited by Different Mechanisms, Carry Out NER Repair Synthesis in Human Cells publication-title: Mol. Cell – volume: 43 start-page: 282 year: 2015 end-page: 294 ident: 2023.10.11.561854v2.21 article-title: Roles of PCNA ubiquitination and TLS polymerases κ and η in the bypass of methyl methanesulfonate-induced DNA damage publication-title: Nucleic Acids Res – volume: 22 start-page: 6621 year: 2003 end-page: 6630 ident: 2023.10.11.561854v2.26 article-title: Mouse Rev1 protein interacts with multiple DNA polymerases involved in translesion DNA synthesis publication-title: EMBO J – volume: 21 start-page: 15 year: 2006 end-page: 27 ident: 2023.10.11.561854v2.75 article-title: Multiple Mechanisms Control Chromosome Integrity ater Replication Fork Uncoupling and Restart at Irreparable UV Lesions publication-title: Mol. Cell – volume: 265 start-page: 2096 year: 1994 end-page: 2098 ident: 2023.10.11.561854v2.64 article-title: Alignment and sensitive detection of DNA by a moving interface publication-title: Science – volume: 47 start-page: 497 year: 2012 end-page: 510 ident: 2023.10.11.561854v2.62 article-title: Playing the end game: DNA double-strand break repair pathway choice publication-title: Mol. Cell – volume: 168 start-page: 644 year: 2017 end-page: 656 ident: 2023.10.11.561854v2.1 article-title: Endogenous DNA Damage as a Source of Genomic Instability in Cancer publication-title: Cell – volume: 33 start-page: 1280 year: 2005 end-page: 1289 ident: 2023.10.11.561854v2.25 article-title: Vertebrate DNA damage tolerance requires the C-terminus but not BRCT or transferase domains of REV1 publication-title: Nucleic Acids Res – volume: 87 start-page: 239 year: 2018 end-page: 261 ident: 2023.10.11.561854v2.29 article-title: Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism publication-title: Annu. Rev. Biochem – volume: 42 start-page: 112887 year: 2023 ident: 2023.10.11.561854v2.79 article-title: Spontaneous mutagenesis in human cells is controlled by REV1-Polymerase ζ and PRIMPOL publication-title: Cell Rep – volume: 50 start-page: 7420 year: 2022 end-page: 7435 ident: 2023.10.11.561854v2.36 article-title: Division of labor within the DNA damage tolerance system reveals non-epistatic and clinically actionable targets for precision cancer medicine publication-title: Nucleic Acids Res – volume: 10 year: 2019 ident: 2023.10.11.561854v2.57 article-title: Mutating for Good: DNA Damage Responses During Somatic Hypermutation publication-title: Front. Immunol – volume: 5 start-page: 17 year: 1993 end-page: 21 ident: 2023.10.11.561854v2.65 article-title: High resolution visual mapping of stretched DNA by fluorescent hybridization publication-title: Nat. Genet – volume: 49 start-page: 4831 year: 2021 end-page: 4847 ident: 2023.10.11.561854v2.67 article-title: Repriming DNA synthesis: an intrinsic restart pathway that maintains efficient genome replication publication-title: Nucleic Acids Res – volume: 30 start-page: 519 year: 2008 end-page: 529 ident: 2023.10.11.561854v2.24 article-title: PCNA Ubiquitination and REV1 Define Temporally Distinct Mechanisms for Controlling Translesion Synthesis in the Avian Cell Line DT40 publication-title: Mol. Cell – year: 2015 ident: 2023.10.11.561854v2.60 publication-title: Concepts of genetics Eleventh edition – volume: 9 start-page: 18832 year: 2018 end-page: 18843 ident: 2023.10.11.561854v2.46 article-title: Precision cancer therapy: Profiting from tumor specific defects in the DNA damage tolerance system publication-title: Oncotarget – volume: 447 start-page: 725 year: 2007 end-page: 729 ident: 2023.10.11.561854v2.4 article-title: Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age publication-title: Nature – volume: 114 start-page: E6875 year: 2017 end-page: E6883 ident: 2023.10.11.561854v2.7 article-title: DNA damage tolerance in hematopoietic stem and progenitor cells in mice publication-title: Proc. Natl. Acad. Sci. U. S. A – volume: 47 start-page: 5243 year: 2019 end-page: 5259 ident: 2023.10.11.561854v2.58 article-title: Mammalian CST averts replication failure by preventing G-quadruplex accumulation publication-title: Nucleic Acids Res – volume: 559 start-page: 279 year: 2018 end-page: 284 ident: 2023.10.11.561854v2.74 article-title: High speed of fork progression induces DNA replication stress and genomic instability publication-title: Nature – volume: 1 start-page: 1 year: 2017 end-page: 16 ident: 2023.10.11.561854v2.13 article-title: How DNA polymerases catalyse replication and repair with contrasting fidelity publication-title: Nat. Rev. Chem – volume: 14 start-page: 269 year: 2013 end-page: 282 ident: 2023.10.11.561854v2.28 article-title: Regulation of PCNA–protein interactions for genome stability publication-title: Nat. Rev. Mol. Cell Biol |
| SSID | ssj0002961374 |
| Score | 1.7043499 |
| SecondaryResourceType | preprint |
| Snippet | DNA damage tolerance (DDT) enables replication to continue in the presence of fork stalling lesions. To determine the molecular and genomic impact of a global... |
| SourceID | biorxiv proquest |
| SourceType | Open Access Repository Aggregation Database |
| SubjectTerms | CRISPR DNA damage Genomes Genomics Genotoxicity Molecular Biology Mutants Replication Whole genome sequencing |
| Title | Molecular dependencies and genomic consequences of a global DNA damage tolerance defect |
| URI | https://www.proquest.com/docview/2886455548 https://www.biorxiv.org/content/10.1101/2023.10.11.561854 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3db9MwELdgBYk3PsXYmIyEeKkyFufD9uMYnUB0IZo6UZ4iJ7a1jpF0aZnKf8_5o2lQJQQPvES1o8bR3S_22fe7O4ReS2F8Y-lRoCiXQaxVFDDYhgSKhCKGBZmSSttiEzTL2HTKc3-Ys7DlBGhds9WKz_-rqqEPlG1CZ_9B3d1DoQN-g9LhCmqH618p_mxd8Ha4LnALn6_LxGwSshoufNWjULsASZ8X5H12PJTiu-HxLOExrY0nkMpQPvpWbDlrzlez2w13p2mWm3h1mMM2PnlRXwnh6PPH17LpblyKS0fsrkUXK_QJVmsfQCRm31T_QIJENjIv7SB00lyDpWxPJU0gEiB5OHZ4NqSBPrEE5jiScpiQyZFzbKvtvu0Z3lYWMOMe2uYhGIDM5aH-PZt29rk4vRiPi8loOnkzvwlMoTHjkPdVV-6iAaEJh4lw8G6U5efdwRzhYOHY7N3di3hvOAz9dmtg2DeB0FsQ-tZqbk2UyUM0yMVctY_QHVU_RvddjdGfT9CXDg-4jwcMeMAeD7iPB9xoLLDDAwY8YIcH3OEBOzw8RReno8nJh8BX0whK2HLHQam0FqUWVMaKRJQrWuo4CQVnCVWRVGGskiqiMpWhJGmpSUIqUjGiqeaJZCR6hnbqplbPETY1yLQMSxVyZhL2cRpV9r_QqGTEdtErL5Ni7nKmFEZuhd1wFk5uu2h_La3Cfz2LgjCWxglYuOzFn2_voQcb6O2jnWX7Q71E96rb5WzRHniVHhgibw6t_ONZ_vUXKdZq1g |
| linkProvider | ProQuest |
| 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=Molecular+dependencies+and+genomic+consequences+of+a+global+DNA+damage+tolerance+defect&rft.jtitle=bioRxiv&rft.au=Groot%2C+Daniel+De&rft.au=Spanjaard%2C+Aldo&rft.au=Shah%2C+Ronak&rft.au=Kreft%2C+Maaike&rft.date=2023-11-06&rft.pub=Cold+Spring+Harbor+Laboratory+Press&rft.issn=2692-8205&rft.eissn=2692-8205&rft_id=info:doi/10.1101%2F2023.10.11.561854&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2692-8205&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2692-8205&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2692-8205&client=summon |