Transcription-coupled nucleotide excision repair in mammalian cells： molecular mechanisms and biological effects  

作　　者：Mafia Fousteri Leon HF Mullenders 

机构地区：[1]Department of Toxicogenetics, Leiden University Medical Center, E inthovenweg 20, 2333 ZC, Leiden, The Netherlands

出　　处：《Cell Research》2008年第1期73-84,共12页细胞研究（英文版）

摘　　要：The encounter of elongating RNA polymerase Ⅱ （RNAPⅡo） with DNA lesions has severe consequences for the cell as this event provides a strong signal for P53-dependent apoptosis and cell cycle arrest. To counteract prolonged blockage of transcription, the cell removes the RNAPⅡo-blocking DNA lesions by transcription-coupled repair （TC-NER）, a specialized subpathway of nucleotide excision repair （NER）. Exposure of mice to UVB light or chemicals has elucidated that TC-NER is a critical survival pathway protecting against acute toxic and long-term effects （cancer） of genotoxic exposure. Deficiency in TC-NER is associated with mutations in the CSA and CSB genes giving rise to the rare human disorder Cockayne syndrome （CS）. Recent data suggest that CSA and CSB play differential roles in mammalian TC-NER： CSB as a repair coupling factor to attract NER proteins, chromatin remodellers and the CSA- E3-ubiquitin ligase complex to the stalled RNAPⅡo. CSA is dispensable for attraction of NER proteins, yet in cooperation with CSB is required to recruit XAB2, the nucleosomal binding protein HMGN1 and TFⅡS. The emerging picture of TC-NER is complex： repair of transcription-blocking lesions occurs without displacement of the DNA damage-stalled RNAPⅡo, and requires at least two essential assembly factors （CSA and CSB）, the core NER factors （except for XPC-RAD23B）, and TC-NER specific factors. These and yet unidentified proteins will accomplish not only efficient repair of transcription-blocking lesions, but are also likely to contribute to DNA damage signalling events.

关 键 词：DNA damage TRANSCRIPTION nucleotide excision repair transcription coupled repair Cockayne syndrome chromatin remodelling 

分 类 号：Q25[生物学—细胞生物学]