Model for XPC-independent transcription-coupled repair of pyrimidine dimers in humans
Model for XPC-independent transcription-coupled repair of pyrimidine dimers in humans
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DOI：
10.1074/jbc.272.12.7570
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发表时间：
1997-03-21
影响因子：
4.8
通讯作者：
Sancar, A
中科院分区：
文献类型：
--
作者：
Mu, D;Sancar, A
在人类中，由RNA聚合酶II转录的基因模板链中的嘧啶二聚体等DNA损伤比基因组的编码链和非转录区修复得更快。这种现象被称为转录偶联修复(i)需要主动转录，（ii）不需要一般/基础修复反应所必需的XPC基因产物，（iii）需要CSA和CSB蛋白。我们开发了一种体外模型系统，由纯化的人类切除修复因子和类似于转录泡终止于环丁烷胸腺嘧啶二聚体的DNA底物组成。在该系统中，胸腺嘧啶二聚体的切除不依赖于XPC。此外，与用整套切除核酸酶因子从碱基配对的双工中去除胸腺嘧啶二聚体相比，用XPC或不含XPC重组的切除核酸酶去除含气泡底物中的胸腺嘧啶二聚体的速度快约3倍。这些结果为人类转录偶联修复的机制提供了重要的认识。
In humans, DNA lesions such as pyrimidine dimers in the template strand of genes transcribed by RNA polymerase II are repaired faster than those in the coding strand and nontranscribed regions of the genome. This phenomenon, referred to as transcription-coupled repair (i) requires active transcription, (ii) does not require the XPC gene product which is essential for general/basal repair reactions, and (iii) requires the CSA and CSB proteins. We have developed an in vitro model system that consists of purified human excision repair factors and a DNA substrate analogous to a transcription bubble terminating at a cyclobutane thymine dimer. In this system the thymine dimer was excised independent of XPC, Furthermore, the thymine dimer in the bubble-containing substrate was removed approximately 3-fold faster by the excision repair nuclease reconstituted with or without XPC, compared with the removal of thymine dimer from a base paired duplex by the entire set of excision nuclease factors, These results provide important insight into the mechanism of transcription-coupled repair in humans.