Publication Date:
2010-06-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pace, Paul -- Mosedale, Georgina -- Hodskinson, Michael R -- Rosado, Ivan V -- Sivasubramaniam, Meera -- Patel, Ketan J -- MC_U105178811/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):219-23. doi: 10.1126/science.1192277. Epub 2010 Jun 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20538911" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, Nuclear/*genetics/metabolism
;
Cell Line
;
Chickens
;
Chromosome Breakage
;
Cross-Linking Reagents/pharmacology
;
*DNA Breaks, Double-Stranded
;
*DNA Repair
;
DNA-Binding Proteins/*genetics/metabolism
;
Fanconi Anemia Complementation Group C Protein/*genetics/metabolism
;
Fanconi Anemia Complementation Group D2 Protein/chemistry/genetics/*metabolism
;
Gene Conversion
;
Genes, Immunoglobulin
;
Humans
;
Immunoglobulin M/genetics
;
Point Mutation
;
Recombinant Proteins/metabolism
;
*Recombination, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
