FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end

Koichi Sato, Mayo Shimomuki, Yoko Katsuki, Daisuke Takahashi, Wataru Kobayashi, Masamichi Ishiai, Hiroyuki Miyoshi, Minoru Takata, Hitoshi Kurumizaka

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

The FANCI-FANCD2 (I-D) complex is considered to work with RAD51 to protect the damaged DNA in the stalled replication fork. However, the means by which this DNA protection is accomplished have remained elusive. In the present study, we found that the I-D complex directly binds to RAD51, and stabilizes the RAD51-DNA filament. Unexpectedly, the DNA binding activity of FANCI, but not FANCD2, is explicitly required for the I-D complex-mediated RAD51-DNA filament stabilization. The RAD51 filament stabilized by the I-D complex actually protects the DNA end from nucleolytic degradation by an FA-Associated nuclease, FAN1. This DNA end protection is not observed with the RAD51 mutant from FANCR patient cells. These results clearly answer the currently enigmatic question of how RAD51 functions with the I-D complex to prevent genomic instability at the stalled replication fork.

Original languageEnglish
Pages (from-to)10758-10771
Number of pages14
JournalNucleic acids research
Volume44
Issue number22
DOIs
Publication statusPublished - 2016 Dec

ASJC Scopus subject areas

  • Genetics

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