RRC ID 54483
Author Sato K, Shimomuki M, Katsuki Y, Takahashi D, Kobayashi W, Ishiai M, Miyoshi H, Takata M, Kurumizaka H.
Title FANCI-FANCD2 stabilizes the RAD51-DNA complex by binding RAD51 and protects the 5'-DNA end.
Journal Nucleic Acids Res.
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.
Volume 44(22)
Pages 10758-10771
Published 2016-12-15
DOI 10.1093/nar/gkw876
PII gkw876
PMID 27694619
PMC PMC5159555
MeSH Amino Acid Sequence Animals Avian Proteins / physiology* Cell Line, Tumor Chickens Conserved Sequence DNA / genetics* DNA / metabolism DNA Damage DNA Repair DNA Replication Fanconi Anemia Complementation Group D2 Protein / physiology* Genomic Instability Humans Protein Binding Protein Stability Rad51 Recombinase / physiology* Ubiquitination
IF 11.561
Resource
DNA material CSIV-TRE-RfA-UbC-KT (RDB12878)