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Science. 2010 Jul 9;329(5988):219-23. doi: 10.1126/science.1192277. Epub 2010 Jun 10.

Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.

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1
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.

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.

PMID:
20538911
DOI:
10.1126/science.1192277
[Indexed for MEDLINE]
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