title: BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade.
abstract: Breast cancer gene 1 (BRCA1) deficient cells not only are hypersensitive to double-strand breaks but also are hypersensitive to UV irradiation and other agents that cause replication blockade; however, the molecular mechanisms behind these latter sensitivities are largely unknown. Here, we report that BRCA1 promotes cell survival by directly regulating the DNA damage tolerance pathway in response to agents that create cross-links in DNA. We show that BRCA1 not only promotes efficient mono- and polyubiquitination of proliferating cell nuclear antigen (PCNA) by regulating the recruitment of replication protein A, Rad18, and helicase-like transcription factor to chromatin but also directly recruits translesion polymerases, such as Polymerase eta and Rev1, to the lesions through protein-protein interactions. Our data suggest that BRCA1 plays a critical role in promoting translesion DNA synthesis as well as DNA template switching.
authors.affiliation: Basic Biomedical Science Division, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
authors.forename: Fen
authors.initials: F
authors.lastname: Tian
authors.forename: Shilpy
authors.initials: S
authors.lastname: Sharma
authors.forename: Jianqiu
authors.initials: J
authors.lastname: Zou
authors.forename: Shiaw-Yih
authors.initials: SY
authors.lastname: Lin
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Khosrow
authors.initials: K
authors.lastname: Rezvani
authors.forename: Hongmin
authors.initials: H
authors.lastname: Wang
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Parvin
authors.forename: Thomas
authors.initials: T
authors.lastname: Ludwig
authors.forename: Christine E
authors.initials: CE
authors.lastname: Canman
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism* / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051716:Replication Protein A / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination; D000099270:Y-Family DNA Polymerases
chemical_list: D019313:BRCA1 Protein; D002843:Chromatin; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D051716:Replication Protein A; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; C492913:BRCA1 protein, human; C100023:HLTF protein, human; C485954:RAD18 protein, human; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases
references.citation: DNA Repair (Amst). 2010 Mar 2;9(3):257-67
references.pmid: 20096653
references.citation: Mol Cell Biol. 2001 Nov;21(21):7199-206
references.pmid: 11585903
references.citation: Nat Chem Biol. 2008 Feb;4(2):119-25
references.pmid: 18176557
references.citation: Mol Cell. 2011 Sep 2;43(5):788-97
references.pmid: 21884979
references.citation: J Cell Biol. 2006 Dec 4;175(5):703-8
references.pmid: 17130289
references.citation: Cancer Res. 2001 Jun 15;61(12):4842-50
references.pmid: 11406561
references.citation: Mol Cells. 2008 Jul 31;26(1):5-11
references.pmid: 18525240
references.citation: Mol Cell Biol. 2008 Dec;28(24):7380-93
references.pmid: 18936166
references.citation: Nat Rev Mol Cell Biol. 2010 Feb;11(2):138-48
references.pmid: 20029420
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18107-12
references.pmid: 17108083
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6484-9
references.pmid: 15096610
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3768-73
references.pmid: 18316726
references.citation: Science. 2005 Dec 16;310(5755):1821-4
references.pmid: 16357261
references.citation: Genes Dev. 2006 Jan 1;20(1):34-46
references.pmid: 16391231
references.citation: Nature. 2004 Mar 4;428(6978):97-100
references.pmid: 14999287
references.citation: Cancer Res. 2003 Oct 1;63(19):6221-8
references.pmid: 14559807
references.citation: Science. 1999 Feb 12;283(5404):1001-4
references.pmid: 9974380
references.citation: Nat Chem Biol. 2009 Feb;5(2):82-90
references.pmid: 19148176
references.citation: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5646-51
references.pmid: 12732733
references.citation: DNA Repair (Amst). 2009 Apr 5;8(4):461-9
references.pmid: 19217833
references.citation: Carcinogenesis. 2010 Jun;31(6):961-7
references.pmid: 20400477
references.citation: Mol Cell. 2008 Mar 14;29(5):625-36
references.pmid: 18342608
references.citation: Genes Dev. 2003 Jan 15;17(2):201-13
references.pmid: 12533509
references.citation: Genes Dev. 2002 Jan 15;16(2):198-208
references.pmid: 11799063
references.citation: Genes Dev. 2008 May 1;22(9):1147-52
references.pmid: 18451105
references.citation: Mol Cell. 1999 Oct;4(4):511-8
references.pmid: 10549283
references.citation: Cell Div. 2008 Jan 07;3:1
references.pmid: 18179693
references.citation: Mol Cell. 2004 May 21;14(4):491-500
references.pmid: 15149598
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12411-6
references.pmid: 18719106
references.citation: Mol Cell. 2010 Oct 22;40(2):179-204
references.pmid: 20965415
references.citation: Mol Cell. 2011 Apr 22;42(2):237-49
references.pmid: 21396873
references.citation: Cancer Res. 2005 Nov 1;65(21):9799-806
references.pmid: 16267001
references.citation: Science. 2011 Oct 28;334(6055):525-8
references.pmid: 22034435
references.citation: J Biochem. 2010 Nov;148(5):539-47
references.pmid: 20679368
references.citation: Mol Cell Biol. 2010 Mar;30(5):1217-30
references.pmid: 20028736
references.citation: J Biol Chem. 2000 Aug 4;275(31):23899-903
references.pmid: 10843985
references.citation: Nat Struct Mol Biol. 2004 Jun;11(6):512-8
references.pmid: 15133502
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16125-30
references.pmid: 18845679
references.citation: Cell. 2002 May 17;109(4):459-72
references.pmid: 12086603