BRCA1 and CtIP suppress long tract gene conversion between sister chromatids
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CitationChandramouly, Gurushankar, Amy Kwok, Bin Huang, Nicholas A. Willis, Anyong Xie, and Ralph Scully. 2013. “BRCA1 and CtIP suppress long tract gene conversion between sister chromatids.” Nature communications 4 (1): 10.1038/ncomms3404. doi:10.1038/ncomms3404. http://dx.doi.org/10.1038/ncomms3404.
AbstractBRCA1 controls early steps of the synthesis-dependent strand annealing (SDSA) pathway of homologous recombination, but has no known role following Rad51-mediated synapsis. Here we show that BRCA1 influences post-synaptic homologous recombination events, controlling the balance between short- (STGC) and long-tract gene conversion (LTGC) between sister chromatids. Brca1 mutant cells reveal a bias towards LTGC that is corrected by expression of wild type but not cancer-predisposing BRCA1 alleles. The LTGC bias is enhanced by depletion of CtIP but reversed by inhibition of 53BP1, implicating DNA end resection as a contributor to the STGC/LTGC balance. The impact of BRCA1/CtIP loss on the STGC/LTGC balance is abolished when the second (non-invading) end of the break is unable to support termination of STGC by homologous pairing (“annealing”). This suggests that BRCA1/CtIP-mediated processing of the second end of the break controls the annealing step that normally terminates SDSA, thereby suppressing the error-prone LTGC outcome.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12064511
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