Mechanism of RAD51-dependent DNA interstrand cross-link repair.
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.
PubMed ID: 21719678
PMC ID: PMC4068331
Article link: Science.
Grant support: GM80676 NIGMS NIH HHS , HL098316 NHLBI NIH HHS , R01 HL098316 NHLBI NIH HHS
Genes referenced: fancd2 fanci rad51