The role of BRCA2 in replication-coupled DNA interstrand cross-link repair in vitro

Lubos Cipak, Norifumi Watanabe, Tadayoshi Bessho

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Using a defined substrate DNA with a single psoralen interstrand cross-link (ICL), we studied the molecular mechanism of human ICL repair. In vitro ICL repair by human extracts is dependent on replication and is a largely error-free process. Extracts from a human BRCA2-defective mutant cell line, CAPAN-1, are severely compromised in ICL repair. Specifically, 'unhooked' but not fully repaired products accumulate in the reaction with CAPAN-1, and transient expression of BRCA2 in CAPAN-1 restores repair activity. Together, these results reveal that BRCA2 participates in repair of replication-mediated double-strand breaks generated when replication forks encounter ICLs. We also show that nucleotide excision repair is essential for the removal of the lesion left behind on one strand after unhooking. This study provides new mechanistic insights into the repair of ICLs in human cells.

Original languageEnglish (US)
Pages (from-to)729-733
Number of pages5
JournalNature Structural and Molecular Biology
Volume13
Issue number8
DOIs
StatePublished - Aug 2006

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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