Nucleotide excision repair and homologous recombination systems commit differentially to the repair of DNA-Protein crosslinks
Nucleotide excision repair and homologous recombination systems commit differentially to the repair of DNA-Protein crosslinks
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DOI：
10.1016/j.molcel.2007.07.029
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发表时间：
2007-10-12
期刊：
影响因子：
16
通讯作者：
Ide, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakano, Toshiaki;Morishita, Soh;Ide, Hiroshi
DNA-蛋白质交联（DPC）-蛋白质被共价捕获在DNA链上，阻止复制和转录机制的进展，从而阻碍遗传信息的忠实传递。然而，DPC的修复机制在很大程度上仍然难以捉摸。在这里，我们已经分析了核苷酸切除修复（NER）和同源重组（HR）在修复的DPC在体外和体内使用细菌系统的作用。几条生化和遗传证据表明，NER和HR都致力于DPC的修复或耐受，但存在差异。NER修复DPC与交联蛋白的大小小于12-14 kDa，而过大的DPC是专门由RecBCD依赖的HR处理。这些结果突出了NER和HR是如何协调时，细胞需要处理异常庞大的DNA病变，如DPC。
DNA-protein crosslinks (DPCs)-where proteins are covalently trapped on the DNA strandblock the progression of replication and transcription machineries and hence hamper the faithful transfer of genetic information. However, the repair mechanism of DPCs remains largely elusive. Here we have analyzed the roles of nucleotide excision repair (NER) and homologous recombination (HR) in the repair of DPCs both in vitro and in vivo using a bacterial system. Several lines of biochemical and genetic evidence show that both NER and HR commit to the repair or tolerance of DPCs, but differentially. NER repairs DPCs with crosslinked proteins of sizes less than 12-14 kDa, whereas oversized DPCs are processed exclusively by RecBCDdependent HR. These results highlight how NER and HR are coordinated when cells need to deal with unusually bulky DNA lesions such as DPCs.