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

被引：40

作者：

Cipak, Lubos ^{[1
]}

Watanabe, Norifumi ^{[1
]}

Bessho, Tadayoshi ^{[1
]}

机构：

[1] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2006年 / 13卷 / 08期

关键词：

D O I：

10.1038/nsmb1120

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：729 / 733

页数：5

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