title: BRCA1 contributes to transcription-coupled repair of DNA damage through polyubiquitination and degradation of Cockayne syndrome B protein.
abstract: BRCA1 is an important gene involved in susceptibility to breast and ovarian cancer and its product regulates the cellular response to DNA double-strand breaks. Here, we present evidence that BRCA1 also contributes to the transcription-coupled repair (TCR) of ultraviolet (UV) light-induced DNA damage. BRCA1 immediately accumulates at the sites of UV irradiation-mediated damage in cell nuclei in a manner that is fully dependent on both Cockayne syndrome B (CSB) protein and active transcription. Suppression of BRCA1 expression inhibits the TCR of UV lesions and increases the UV sensitivity of cells proficient in TCR. BRCA1 physically interacts with CSB protein. BRCA1 polyubiquitinates CSB and this polyubiquitination and subsequent degradation of CSB occur following UV irradiation, even in the absence of Cockayne syndrome A (CSA) protein. The depletion of BRCA1 expression increases the UV sensitivity of CSA-deficient cells. These results indicate that BRCA1 is involved in TCR and that a BRCA1-dependent polyubiquitination pathway for CSB exists alongside the CSA-dependent pathway to yield more efficient excision repair of lesions on the transcribed DNA strand.
authors.affiliation: Department of Molecular Immunology, Tohoku University, Sendai.
authors.forename: Leizhen
authors.initials: L
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Lan
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Saijo
authors.forename: Ayako
authors.initials: A
authors.lastname: Matsuzawa
authors.forename: Risa
authors.initials: R
authors.lastname: Kashiwagi
authors.forename: Emiko
authors.initials: E
authors.lastname: Maseki
authors.forename: Yiheng
authors.initials: Y
authors.lastname: Hu
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Parvin
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
authors.forename: Natsuko
authors.initials: N
authors.lastname: Chiba
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D034622:RNA Interference; D034741:RNA, Small Interfering; D014157:Transcription Factors; D057149:Ubiquitinated Proteins / Q000378:metabolism; D054875:Ubiquitination; D014466:Ultraviolet Rays
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C095472:ERCC8 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D057149:Ubiquitinated Proteins; D004247:DNA; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes