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

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

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)147-158
Number of pages12
JournalMolecular Cell
Volume28
Issue number1
DOIs
Publication statusPublished - Oct 12 2007
Externally publishedYes

Keywords

  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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