Initiation of DNA repair mediated by a stalled RNA polymerase IIO
Initiation of DNA repair mediated by a stalled RNA polymerase IIO
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DOI：
10.1038/sj.emboj.7600933
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发表时间：
2006-01-25
期刊：
影响因子：
11.4
通讯作者：
Egly, JM
中科院分区：
文献类型：
--
作者：
Lainé, JP;Egly, JM
转录偶联修复（TCR）途径优先修复位于活性基因的转录链中的DNA损伤。为了深入了解转录和修复之间的耦合机制，我们已经建立了一个体外系统，在该系统中，我们分离出一个延长RNA聚合物IIO，这是停滞在前面的顺铂加合物。这种固定的RNA pol IIO用作“诱饵”，以ATP依赖性方式依次募集TFIIH、XPA、RPA、XPG和XPF修复因子。这种RNA pol IIO/修复复合物仅在CSB存在下允许ATP依赖性去除病变，而后者不促进XC依赖性核苷酸切除修复反应中的双切口。与双切口平行，修复因子也允许RNA pol IIO的部分释放。在这种“最小TCR系统”中，RNA pol IIO可以有效地充当消除转录阻断病变所需的所有修复因子的加载点。
The transcription-coupled repair (TCR) pathway preferentially repairs DNA damage located in the transcribed strand of an active gene. To gain insight into the coupling mechanism between transcription and repair, we have set up an in vitro system in which we isolate an elongating RNA pol IIO, which is stalled in front of a cisplatin adduct. This immobilized RNA pol IIO is used as 'bait' to sequentially recruit TFIIH, XPA, RPA, XPG and XPF repair factors in an ATP-dependent manner. This RNA pol IIO/repair complex allows the ATP-dependent removal of the lesion only in the presence of CSB, while the latter does not promote dual incision in an XPC-dependent nucleotide excision repair reaction. In parallel to the dual incision, the repair factors also allow the partial release of RNA pol IIO. In this 'minimal TCR system', the RNA pol IIO can effectively act as a loading point for all the repair factors required to eliminate a transcription-blocking lesion.