MDC1 interacts with Rad51 and facilitates homologous recombination.
Mediator of DNA damage checkpoint protein-1 (MDC1) is a recently identified nuclear protein that participates in DNA-damage sensing and signaling. Here we report that knockdown of MDC1 by RNA interference results in cellular hypersensitivity to the DNA cross-linking agent mitomycin C and ionizing radiation and in impaired homology-mediated repair of double-strand breaks in DNA. MDC1 forms a complex with Rad51 through a direct interaction with the forkhead-associated domain of MDC1, not the BRCA1 C-terminal domain. Depletion of MDC1 results in impaired formation of Rad51 ionizing radiation-induced foci, reduced amounts of nuclear and chromatin-bound Rad51, and a corresponding increase in Rad51 protein degradation. Together, our findings suggest that MDC1 functions in Rad51-mediated homologous recombination by retaining Rad51 in chromatin.
Pubmed ID: 16186822 RIS Download
BRCA1 Protein | Cell Cycle | Cell Nucleus | Chromatin | DNA Repair | DNA-Binding Proteins | Enzyme Stability | Gene Silencing | Humans | Nuclear Proteins | Rad51 Recombinase | Radiation Tolerance | Radiation, Ionizing | Recombination, Genetic | Trans-Activators