Open AccessBRCA1 contributes to transcription‐coupled repair of DNA damage through polyubiquitination and degradation of Cockayne syndrome B protein
Author(s) -
Wei Leizhen,
Lan Li,
Yasui Akira,
Tanaka Kiyoji,
Saijo Masafumi,
Matsuzawa Ayako,
Kashiwagi Risa,
Maseki Emiko,
Hu Yiheng,
Parvin Jeffrey D.,
Ishioka Chikashi,
Chiba Natsuko
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.02037.x
Subject(s) - cockayne syndrome , dna damage , dna repair , biology , transcription (linguistics) , ubiquitin , nucleotide excision repair , transcription factor , microbiology and biotechnology , dna , cancer research , gene , genetics , linguistics , philosophy
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. ( Cancer Sci 2011; 102: 1840–1847)