Nucleotide Excision Repair and Homologous Recombination Systems Commit Differentially to the Repair of DNA-Protein Crosslinks

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• 作者：Toshiaki Nakano ; Soh Morishita ; Atsushi Katafuchi ; Mayumi Matsubara ; Yusuke Horikawa ; Hiroaki Terato ; Amir M.H. Salem ; Shunsuke Izumi ; Seung Pil Pack ; Keisuke Makino ; Hiroshi Ide
• 关键词：DNA ; PROTEINS
• 刊名：Molecular Cell
• 出版年：2007
• 出版时间：12 October 2007
• 年：2007
• 卷：28
• 期：1
• 页码：147-158
• 全文大小：1069 K

文摘

DNA-protein crosslinks (DPCs)—where proteins are covalently trapped on the DNA strand—block 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 RecBCD-dependent HR. These results highlight how NER and HR are coordinated when cells need to deal with unusually bulky DNA lesions such as DPCs.