Sarasin Alain, Stary Anne
Genomes and Cancers, Institut Gustave Roussy, CNRS FRE 2939, 39, rue Camille Desmoulins, 94805 Villejuif, France.
DNA Repair (Amst). 2007 Feb 4;6(2):265-9. doi: 10.1016/j.dnarep.2006.12.001. Epub 2006 Dec 27.
Transcription-coupled repair (TCR) is a sub-pathway of nucleotide excision repair (NER) able to remove bulky DNA lesions located on the transcribed strands of active genes more rapidly than those located on the non-transcribed genomic DNA. Two recently published reports try to dissect the molecular mechanisms of TCR using simplified in vitro assays. A third report shows in vivo data that confirmed the in vitro ones and extends them to the role of other TCR factors such as those involved in chromatin remodeling. These approaches shed light on the interplay between stalled RNA polymerase II and NER factors necessary for efficient repair. Because severe diseases, such as Cockayne syndrome, are associated with defects or mutations in proteins required for transcription-coupled nucleotide excision repair, complete understanding of this pathway should allow us to understand this disease better and eventually to propose adequate therapies.
转录偶联修复(TCR)是核苷酸切除修复(NER)的一个子途径,它能够比位于非转录基因组DNA上的大片段DNA损伤更快地去除位于活跃基因转录链上的大片段DNA损伤。最近发表的两篇报告试图通过简化的体外试验来剖析TCR的分子机制。第三篇报告展示了体内数据,证实了体外数据,并将其扩展到其他TCR因子的作用,如参与染色质重塑的因子。这些方法揭示了停滞的RNA聚合酶II与有效修复所需的NER因子之间的相互作用。由于严重疾病,如科凯恩综合征,与转录偶联核苷酸切除修复所需蛋白质的缺陷或突变有关,对这一途径的全面理解应该使我们能够更好地理解这种疾病,并最终提出适当的治疗方法。