Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway.
Science
; 329(5988): 219-23, 2010 Jul 09.
Article
em En
| MEDLINE
| ID: mdl-20538911
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recombinação Genética
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Antígenos Nucleares
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Proteínas de Ligação a DNA
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Reparo do DNA
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Proteína do Grupo de Complementação C da Anemia de Fanconi
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Proteína do Grupo de Complementação D2 da Anemia de Fanconi
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Quebras de DNA de Cadeia Dupla
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article