Deubiquitination of FANCD2 is required for DNA crosslink repair
Monoubiquitination of FANCD2 and PCNA promotes DNA repair. It causes chromatin accumulation of FANCD2 and facilitates PCNA's recruitment of translesion polymerases to stalled replication. USP1, a protease that removes monoubiquitin from FANCD2 and PCNA, was thought to reverse the DNA damage res...
Saved in:
| Published in: | Molecular cell Vol. 28; no. 5; p. 798 |
|---|---|
| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
14.12.2007
|
| Subjects: | |
| ISSN: | 1097-2765 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Monoubiquitination of FANCD2 and PCNA promotes DNA repair. It causes chromatin accumulation of FANCD2 and facilitates PCNA's recruitment of translesion polymerases to stalled replication. USP1, a protease that removes monoubiquitin from FANCD2 and PCNA, was thought to reverse the DNA damage response of these substrates. We disrupted USP1 in chicken cells to dissect its role in a stable genetic system. USP1 ablation increases FANCD2 and PCNA monoubiquitination but unexpectedly results in DNA crosslinker sensitivity. This defective DNA repair is associated with constitutively chromatin-bound, monoubiquitinated FANCD2. In contrast, persistent PCNA monoubiquitination has negligible impact on DNA repair or mutagenesis. USP1 was previously shown to autocleave after DNA damage. In DT40, USP1 autocleavage is not stimulated by DNA damage, and expressing a noncleavable mutant in the USP1 knockout strain partially rescues crosslinker sensitivity. We conclude that efficient DNA crosslink repair requires FANCD2 deubiquitination, whereas FANCD2 monoubiquitination is not dependent on USP1 autocleavage. |
|---|---|
| AbstractList | Monoubiquitination of FANCD2 and PCNA promotes DNA repair. It causes chromatin accumulation of FANCD2 and facilitates PCNA's recruitment of translesion polymerases to stalled replication. USP1, a protease that removes monoubiquitin from FANCD2 and PCNA, was thought to reverse the DNA damage response of these substrates. We disrupted USP1 in chicken cells to dissect its role in a stable genetic system. USP1 ablation increases FANCD2 and PCNA monoubiquitination but unexpectedly results in DNA crosslinker sensitivity. This defective DNA repair is associated with constitutively chromatin-bound, monoubiquitinated FANCD2. In contrast, persistent PCNA monoubiquitination has negligible impact on DNA repair or mutagenesis. USP1 was previously shown to autocleave after DNA damage. In DT40, USP1 autocleavage is not stimulated by DNA damage, and expressing a noncleavable mutant in the USP1 knockout strain partially rescues crosslinker sensitivity. We conclude that efficient DNA crosslink repair requires FANCD2 deubiquitination, whereas FANCD2 monoubiquitination is not dependent on USP1 autocleavage. Monoubiquitination of FANCD2 and PCNA promotes DNA repair. It causes chromatin accumulation of FANCD2 and facilitates PCNA's recruitment of translesion polymerases to stalled replication. USP1, a protease that removes monoubiquitin from FANCD2 and PCNA, was thought to reverse the DNA damage response of these substrates. We disrupted USP1 in chicken cells to dissect its role in a stable genetic system. USP1 ablation increases FANCD2 and PCNA monoubiquitination but unexpectedly results in DNA crosslinker sensitivity. This defective DNA repair is associated with constitutively chromatin-bound, monoubiquitinated FANCD2. In contrast, persistent PCNA monoubiquitination has negligible impact on DNA repair or mutagenesis. USP1 was previously shown to autocleave after DNA damage. In DT40, USP1 autocleavage is not stimulated by DNA damage, and expressing a noncleavable mutant in the USP1 knockout strain partially rescues crosslinker sensitivity. We conclude that efficient DNA crosslink repair requires FANCD2 deubiquitination, whereas FANCD2 monoubiquitination is not dependent on USP1 autocleavage.Monoubiquitination of FANCD2 and PCNA promotes DNA repair. It causes chromatin accumulation of FANCD2 and facilitates PCNA's recruitment of translesion polymerases to stalled replication. USP1, a protease that removes monoubiquitin from FANCD2 and PCNA, was thought to reverse the DNA damage response of these substrates. We disrupted USP1 in chicken cells to dissect its role in a stable genetic system. USP1 ablation increases FANCD2 and PCNA monoubiquitination but unexpectedly results in DNA crosslinker sensitivity. This defective DNA repair is associated with constitutively chromatin-bound, monoubiquitinated FANCD2. In contrast, persistent PCNA monoubiquitination has negligible impact on DNA repair or mutagenesis. USP1 was previously shown to autocleave after DNA damage. In DT40, USP1 autocleavage is not stimulated by DNA damage, and expressing a noncleavable mutant in the USP1 knockout strain partially rescues crosslinker sensitivity. We conclude that efficient DNA crosslink repair requires FANCD2 deubiquitination, whereas FANCD2 monoubiquitination is not dependent on USP1 autocleavage. |
| Author | Takata, Minoru Kuiken, Hendrik J Langevin, Frederic Simpson, Laura J Ohzeki, Mioko Pace, Paul Oestergaard, Vibe H Niedzwiedz, Wojciech Patel, Ketan J Sale, Julian E |
| Author_xml | – sequence: 1 givenname: Vibe H surname: Oestergaard fullname: Oestergaard, Vibe H organization: Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK – sequence: 2 givenname: Frederic surname: Langevin fullname: Langevin, Frederic – sequence: 3 givenname: Hendrik J surname: Kuiken fullname: Kuiken, Hendrik J – sequence: 4 givenname: Paul surname: Pace fullname: Pace, Paul – sequence: 5 givenname: Wojciech surname: Niedzwiedz fullname: Niedzwiedz, Wojciech – sequence: 6 givenname: Laura J surname: Simpson fullname: Simpson, Laura J – sequence: 7 givenname: Mioko surname: Ohzeki fullname: Ohzeki, Mioko – sequence: 8 givenname: Minoru surname: Takata fullname: Takata, Minoru – sequence: 9 givenname: Julian E surname: Sale fullname: Sale, Julian E – sequence: 10 givenname: Ketan J surname: Patel fullname: Patel, Ketan J |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18082605$$D View this record in MEDLINE/PubMed |
| BookMark | eNo1T81OwzAYy2GI_cAbIJQTt5bk65ImJzRtDJCmcYFzlaZfpIy22ZL2wNtTCfDFlmxZ9pLM-tAjIXec5Zxx-XjKu9BabHNgrMyZzhmwGVlwpssMSinmZJnSiTG-FkpfkzlXTIFkYkGedjjW_jL6wfdm8KGnwdH95rjdAfWJRpysiA11IdLdcUNtDCm1vv-arLPx8YZcOdMmvP3jFfncP39sX7PD-8vbdnPIrIByyAC0LJw2a60VrI0VqLiCmlmcRtWFKOWkuZNosHYFYtm4xlqQSjeg6rqAFXn47T3HcBkxDVXn0_S4NT2GMVVSMylgworc_wXHusOmOkffmfhd_V-GH8QAWXk |
| CitedBy_id | crossref_primary_10_1016_j_dnarep_2025_103807 crossref_primary_10_1080_15384101_2016_1138185 crossref_primary_10_1074_jbc_C109_038075 crossref_primary_10_1002_stem_437 crossref_primary_10_1080_15384101_2016_1201621 crossref_primary_10_4161_cc_10_23_18501 crossref_primary_10_1038_s41388_019_0856_9 crossref_primary_10_1056_NEJMra0809889 crossref_primary_10_1016_j_molcel_2014_08_012 crossref_primary_10_1016_j_mrfmmm_2008_11_007 crossref_primary_10_1016_j_mrfmmm_2008_11_004 crossref_primary_10_1016_j_hoc_2009_01_008 crossref_primary_10_1074_jbc_M109_016352 crossref_primary_10_1080_15384101_2016_1209613 crossref_primary_10_1371_journal_ppat_1007442 crossref_primary_10_1016_j_jmb_2010_01_003 crossref_primary_10_1128_MCB_00870_13 crossref_primary_10_15252_embr_202050133 crossref_primary_10_1038_s41594_020_0380_1 crossref_primary_10_1186_s11658_025_00753_3 crossref_primary_10_15252_embj_2022111898 crossref_primary_10_1146_annurev_genet_102108_134222 crossref_primary_10_1021_jm501061a crossref_primary_10_1002_advs_202202437 crossref_primary_10_1101_gad_17020911 crossref_primary_10_1016_j_dnarep_2010_11_004 crossref_primary_10_1016_j_molcel_2014_12_001 crossref_primary_10_1080_10409230903154150 crossref_primary_10_1080_15384101_2015_1120918 crossref_primary_10_1038_s41594_022_00826_3 crossref_primary_10_3390_ijms19102909 crossref_primary_10_1038_s41568_023_00633_y crossref_primary_10_1101_gad_1955310 crossref_primary_10_1093_neuonc_nov091 crossref_primary_10_3390_genes11050585 crossref_primary_10_1016_j_mrrev_2016_06_004 crossref_primary_10_1038_s41417_024_00797_1 crossref_primary_10_1111_febs_13648 crossref_primary_10_1016_j_mrrev_2012_06_002 crossref_primary_10_1002_ctd2_242 crossref_primary_10_26508_lsa_201800162 crossref_primary_10_1016_j_chembiol_2011_08_014 crossref_primary_10_1016_j_febslet_2011_04_078 crossref_primary_10_1128_MCB_01406_12 crossref_primary_10_1111_febs_16077 crossref_primary_10_1042_BSR20222591 crossref_primary_10_1371_journal_pone_0053693 crossref_primary_10_1038_s41467_020_19939_8 crossref_primary_10_1093_hmg_ddr103 crossref_primary_10_1155_2014_435197 crossref_primary_10_1016_j_mrfmmm_2008_12_012 crossref_primary_10_1038_srep25513 crossref_primary_10_1093_nar_gkt467 crossref_primary_10_1002_iub_300 crossref_primary_10_3390_ijms21093036 crossref_primary_10_3389_fgene_2016_00061 crossref_primary_10_1007_s11693_015_9162_1 crossref_primary_10_1074_jbc_RA120_013714 crossref_primary_10_1007_s12013_013_9637_1 crossref_primary_10_1002_1873_3468_12060 crossref_primary_10_5402_2012_146748 crossref_primary_10_1111_cas_14375 crossref_primary_10_1016_j_mrfmmm_2009_03_015 crossref_primary_10_1038_nchembio_1455 crossref_primary_10_1101_gad_195248_112 crossref_primary_10_1016_j_mrfmmm_2017_09_004 crossref_primary_10_1007_s10238_023_01075_4 crossref_primary_10_1038_nature11863 crossref_primary_10_1111_j_1600_0625_2011_01365_x crossref_primary_10_1016_j_mrfmmm_2017_09_006 crossref_primary_10_1038_s41598_017_05325_w crossref_primary_10_1007_s13238_011_1098_y crossref_primary_10_1186_1476_4598_12_91 crossref_primary_10_1146_annurev_biochem_080320_112510 crossref_primary_10_1038_nrm3562 crossref_primary_10_1083_jcb_201101062 crossref_primary_10_1016_j_devcel_2009_01_001 crossref_primary_10_1016_j_mrfmmm_2009_02_003 crossref_primary_10_1038_s41420_019_0185_3 crossref_primary_10_1016_j_molcel_2014_05_001 crossref_primary_10_1074_jbc_M109_095141 crossref_primary_10_1007_s12185_017_2283_4 crossref_primary_10_1016_j_dnarep_2024_103739 crossref_primary_10_1016_j_molcel_2018_10_045 crossref_primary_10_1038_nrm2921 crossref_primary_10_1073_pnas_0807485106 crossref_primary_10_1002_jbt_23864 crossref_primary_10_1182_bloodadvances_2022008284 crossref_primary_10_1038_s41594_021_00576_8 crossref_primary_10_1074_jbc_M808430200 crossref_primary_10_1128_MCB_05058_11 crossref_primary_10_1080_10409238_2019_1687420 crossref_primary_10_1158_1541_7786_MCR_23_0323 crossref_primary_10_4161_cc_22688 crossref_primary_10_1038_s41388_018_0590_8 crossref_primary_10_1186_s12943_015_0311_7 crossref_primary_10_1186_s12964_017_0195_9 crossref_primary_10_1038_emboj_2011_457 crossref_primary_10_1042_BST0380116 crossref_primary_10_1007_s00018_012_1051_0 crossref_primary_10_1042_BST0380087 crossref_primary_10_1093_nar_gkw036 crossref_primary_10_1016_j_mrfmmm_2017_05_003 crossref_primary_10_1128_MCB_00086_09 crossref_primary_10_1038_s41594_022_00820_9 crossref_primary_10_1155_2012_349837 crossref_primary_10_1038_ng_855 crossref_primary_10_1007_s00439_022_02462_9 crossref_primary_10_1016_j_bbcan_2025_189297 crossref_primary_10_1016_j_molcel_2016_11_005 crossref_primary_10_1007_s10495_022_01736_x crossref_primary_10_1038_nrm2731 crossref_primary_10_1016_j_dnarep_2010_09_011 crossref_primary_10_1101_gad_349431_122 crossref_primary_10_1042_BCJ20230284 crossref_primary_10_1002_mrd_23449 crossref_primary_10_1128_MCB_00847_15 crossref_primary_10_1111_j_1530_0277_2008_00673_x crossref_primary_10_1038_s41467_019_10408_5 crossref_primary_10_1038_nature07963 crossref_primary_10_1007_s13277_013_1525_1 crossref_primary_10_3389_fcell_2020_00717 crossref_primary_10_1016_j_molcel_2008_10_009 crossref_primary_10_4061_2010_761217 crossref_primary_10_1007_s12013_013_9635_3 crossref_primary_10_1016_j_mrfmmm_2008_11_018 crossref_primary_10_3109_10409238_2010_502166 crossref_primary_10_3389_fgene_2016_00133 crossref_primary_10_1016_j_cell_2011_07_040 crossref_primary_10_1098_rsob_150018 crossref_primary_10_1158_0008_5472_CAN_13_3109 crossref_primary_10_1016_j_molcel_2008_12_003 crossref_primary_10_1016_j_mrfmmm_2013_01_001 crossref_primary_10_1038_nsmb_1504 crossref_primary_10_1093_nar_gkab892 crossref_primary_10_1016_j_febslet_2011_04_044 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1016/j.molcel.2007.09.020 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Biology |
| ExternalDocumentID | 18082605 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GrantInformation_xml | – fundername: Worldwide Cancer Research grantid: 05-0472 – fundername: NCCDPHP CDC HHS grantid: U58 DP006024 – fundername: Medical Research Council grantid: MC_U105178811 – fundername: Medical Research Council grantid: MC_U105178808 |
| GroupedDBID | --- --K -DZ -~X 0R~ 123 1~5 2WC 4.4 457 4G. 5RE 62- 7-5 AAEDT AAEDW AAHBH AAIKJ AAKRW AAKUH AALRI AAMRU AAVLU AAXUO AAYWO ABDGV ABJNI ABMAC ACGFO ACGFS ACNCT ACVFH ADBBV ADCNI ADEZE ADVLN AEFWE AENEX AEUPX AEXQZ AFFNX AFPUW AFTJW AGCQF AGHFR AGKMS AIGII AITUG AKAPO AKBMS AKRWK AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ APXCP ASPBG AVWKF AZFZN BAWUL CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EFKBS EIF EJD F5P FCP FDB FEDTE FIRID HH5 HVGLF HZ~ IH2 IHE IXB J1W JIG KQ8 L7B M3Z M41 N9A NPM O-L O9- OK1 OZT P2P RIG ROL RPZ SDG SES SSZ TR2 7X8 |
| ID | FETCH-LOGICAL-c527t-22963f9a499824ac5e8182b0ce001b3576b0c1f6eaebf3ee7dfdcc2689d28bb32 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 167 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000251926000013&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1097-2765 |
| IngestDate | Thu Oct 02 14:54:14 EDT 2025 Mon Jul 21 05:44:54 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 5 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c527t-22963f9a499824ac5e8182b0ce001b3576b0c1f6eaebf3ee7dfdcc2689d28bb32 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://www.cell.com/article/S1097276507006326/pdf |
| PMID | 18082605 |
| PQID | 69065222 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_69065222 pubmed_primary_18082605 |
| PublicationCentury | 2000 |
| PublicationDate | 2007-12-14 |
| PublicationDateYYYYMMDD | 2007-12-14 |
| PublicationDate_xml | – month: 12 year: 2007 text: 2007-12-14 day: 14 |
| PublicationDecade | 2000 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Molecular cell |
| PublicationTitleAlternate | Mol Cell |
| PublicationYear | 2007 |
| SSID | ssj0014589 |
| Score | 2.340852 |
| Snippet | Monoubiquitination of FANCD2 and PCNA promotes DNA repair. It causes chromatin accumulation of FANCD2 and facilitates PCNA's recruitment of translesion... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 798 |
| SubjectTerms | Animals Apoptosis Blotting, Western Cell Cycle Chickens Chromatin - metabolism Cisplatin - pharmacology Cross-Linking Reagents - pharmacology DNA Damage - drug effects DNA Damage - physiology DNA Repair - drug effects DNA Repair - physiology Endopeptidases - genetics Endopeptidases - metabolism Fanconi Anemia - genetics Fanconi Anemia - metabolism Fanconi Anemia Complementation Group D2 Protein - genetics Fanconi Anemia Complementation Group D2 Protein - metabolism Gene Expression Regulation Gene Targeting Mitomycin - pharmacology Mutagenesis, Site-Directed Mutation Proliferating Cell Nuclear Antigen - genetics Proliferating Cell Nuclear Antigen - metabolism Protein Processing, Post-Translational Subcellular Fractions Ubiquitin - metabolism Ubiquitin-Specific Proteases Ubiquitination |
| Title | Deubiquitination of FANCD2 is required for DNA crosslink repair |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/18082605 https://www.proquest.com/docview/69065222 |
| Volume | 28 |
| WOSCitedRecordID | wos000251926000013&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEB5WV8GL78f6zMFrtE3TpgVhWXZdvFj2oLC3kqQpFNZ2n4L_3kkfeBIPXkqhFMp0JvNNvsl8APeWq0JfSTGQ_IhyITwqlR13h8HlqRSTvq7FJkQch9NpNOnAU3sWxrZVtmtitVCnpbZ75I92oC5iBdafL6jVjLLcaiOgsQVdD4GM9Wkx_eEQuF8J4FmKlTIR-O3Buaq766OcaTNrRhhGDw5zfoeYVaoZH_zvIw9hv4GYZFD7xBF0THEMu7Xo5NcJ9Edmo_LFJl_n9U4gKTMyHsTDESP5iiyN7Q02KUE0S0bxgFR51PK8-Ggu8-UpvI-f34YvtJFRoNpnYk0ZwyDLIom1Tci41L7BJM2Uow0aSXlYcOC9mwVGGpV5xog0S7VmQRilLFTKY2ewXZSFuQCiuAVcQrg887AS5ArDPTA6ixzNpXRlD-5auyToppZ7kIUpN6uktUwPzmvTJvN6mkbihohCsKi6_PPdK9irdlZdRl1-Dd0MA9TcwI7-XOer5W319_EaT16_AfoYt1s |
| 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=Deubiquitination+of+FANCD2+is+required+for+DNA+crosslink+repair&rft.jtitle=Molecular+cell&rft.au=Oestergaard%2C+Vibe+H&rft.au=Langevin%2C+Frederic&rft.au=Kuiken%2C+Hendrik+J&rft.au=Pace%2C+Paul&rft.date=2007-12-14&rft.issn=1097-2765&rft.volume=28&rft.issue=5&rft.spage=798&rft_id=info:doi/10.1016%2Fj.molcel.2007.09.020&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1097-2765&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1097-2765&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1097-2765&client=summon |