Mechanism of RAD51-Dependent DNA Interstrand Cross-Link Repair

被引：172

作者：

Long, David T. ^{[1
]}

Raeschle, Markus ^{[2
]}

Joukov, Vladimir ^{[3
]}

Walter, Johannes C. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany

[3] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

来源：

SCIENCE | 2011年 / 333卷 / 6038期

关键词：

DOUBLE-STRAND BREAKS; FANCONI-ANEMIA; HOMOLOGOUS RECOMBINATION; JUNCTIONS; PROTEIN;

D O I：

10.1126/science.1204258

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

DNA interstrand cross-links (ICLs) are toxic DNA lesions whose repair in S phase of eukaryotic cells is incompletely understood. In Xenopus egg extracts, ICL repair is initiated when two replication forks converge on the lesion. Dual incisions then create a DNA double-strand break (DSB) in one sister chromatid, whereas lesion bypass restores the other sister. We report that the broken sister chromatid is repaired via RAD51-dependent strand invasion into the regenerated sister. Recombination acts downstream of FANCI-FANCD2, yet RAD51 binds ICL-stalled replication forks independently of FANCI-FANCD2 and before DSB formation. Our results elucidate the functional link between the Fanconi anemia pathway and the recombination machinery during ICL repair. In addition, they demonstrate the complete repair of a DSB via homologous recombination in vitro.

引用

页码：84 / 87

页数：4

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