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A Rad50-dependent pathway of DNA repair is deficient in Fanconi anemia fibroblasts.

Authors: Donahue, SL  Campbell, C 
Citation: Donahue SL and Campbell C, Nucleic Acids Res 2004 Jun 15;32(10):3248-57. Print 2004.
Pubmed: (View Article at PubMed) PMID:15199173
DOI: Full-text: DOI:10.1093/nar/gkh649

Fanconi anemia (FA) is a fatal genetic disorder associated with pancytopenia and cancer. Cells lacking functional FA genes are hypersensitive to bifunctional alkylating agents, and are deficient in DNA double-strand break repair. Multiple genes with FA-causing mutations have been cloned, however, the molecular basis for FA remains obscure. The results presented herein indicate that a Rad50-dependent end-joining process is non-functional in diploid fibroblasts from FA patients. Introduction of anti-Rad50 antibody into normal fibroblasts sensitized them to DNA damaging agents, whereas this treatment had no effect on fibroblasts from FA patients. The DNA end-joining process deficient in FA cells also requires the Mre11, Nbs1 and DNA ligase IV proteins. These data reveal the existence of a previously uncharacterized Rad50-dependent DNA double-strand break repair pathway in mammalian somatic cells, and suggest that failure to activate this pathway is responsible, at least in part, for the defective DNA end-joining observed in FA cells.


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RGD Object Information
RGD ID: 1302871
Created: 2004-11-11
Species: All species
Last Modified: 2004-11-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.