BRCA1 contributes to transcription-coupled repair of DNA damage through polyubiquitination and degradation of Cockayne syndrome B protein.
BRCA1 contributes to transcription-coupled repair of DNA damage through polyubiquitination and degradation of Cockayne syndrome B protein.
复制标题
BRCA1 通过多聚泛素化和 Cockayne 综合征 B 蛋白的降解，有助于 DNA 损伤的转录偶联修复。
DOI：
10.1111/j.1349-7006.2011.02037.x
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发表时间：
2011
期刊：
影响因子：
5.7
通讯作者：
Ishioka C and Chiba N
中科院分区：
文献类型：
--
作者：
Wei L;Lan L;Yasui A;Tanaka K;Saijo M;Matsuzawa A;Kashiwagi R;Maseki E;Hu Y;Parvin J D;Ishioka C and Chiba N
BRCA 1是乳腺癌和卵巢癌易感性的重要基因，其产物调节细胞对DNA双链断裂的反应。在这里，我们提出的证据表明，BRCA 1也有助于紫外线（UV）光诱导的DNA损伤的转录偶联修复（TCR）。BRCA 1以完全依赖于Cockayne综合征B（CS B）蛋白和活性转录的方式立即在细胞核中的紫外线辐射介导的损伤部位积累。BRCA 1表达的抑制抑制了UV损伤的TCR，并增加了精通TCR的细胞的UV敏感性。BRCA 1与CSB蛋白发生物理相互作用。BRCA 1多聚泛素化CSB，这种多聚泛素化和随后的CSB降解发生在紫外线照射后，即使在没有Cockayne综合征A（CSA）蛋白的情况下。BRCA 1表达的缺失增加了CSA缺陷细胞的紫外线敏感性。这些结果表明BRCA 1参与TCR，并且CSB的BRCA 1依赖性多泛素化途径与CSA依赖性途径一起存在，以产生转录DNA链上损伤的更有效切除修复。（Cancer Sci2011; 102：1840-1847）
BRCA1is 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 Sci2011; 102: 1840–1847)