Ku70 corrupts DNA Repair in the Absence of the Fanconi Anemia Pathway

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Science  10 Jun 2010:
DOI: 10.1126/science.1192277


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 crosslinking agents. Here, we reveal 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 crosslinking 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 might antagonise Ku70 activity by modifying such DNA substrates. These results reveal a function for the FA pathway in processing DNA ends, diverting double-strand break repair away from abortive NHEJ and toward homologous recombination.