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.[1]References
- MDC1 interacts with Rad51 and facilitates homologous recombination. Zhang, J., Ma, Z., Treszezamsky, A., Powell, S.N. Nat. Struct. Mol. Biol. (2005) [Pubmed]
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