Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway
- PMID: 20538911
- DOI: 10.1126/science.1192277
Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway
Abstract
A conserved DNA repair response is defective in the human genetic illness Fanconi anemia (FA). Mutation of some FA genes impairs homologous recombination and error-prone DNA repair, rendering FA cells sensitive to DNA cross-linking agents. We found a genetic interaction between the FA gene FANCC and the nonhomologous end joining (NHEJ) factor Ku70. Disruption of both FANCC and Ku70 suppresses sensitivity to cross-linking agents, diminishes chromosome breaks, and reverses defective homologous recombination. Ku70 binds directly to free DNA ends, committing them to NHEJ repair. We show that purified FANCD2, a downstream effector of the FA pathway, might antagonize Ku70 activity by modifying such DNA substrates. These results reveal a function for the FA pathway in processing DNA ends, thereby diverting double-strand break repair away from abortive NHEJ and toward homologous recombination.
Comment in
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Dangerous liaisons: Fanconi anemia and toxic nonhomologous end joining in DNA crosslink repair.Mol Cell. 2010 Jul 30;39(2):164-6. doi: 10.1016/j.molcel.2010.07.016. Mol Cell. 2010. PMID: 20670885 Free PMC article.
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