BRCA1 and CtIP suppress long tract gene conversion between sister chromatids
Citation
Chandramouly, 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.Abstract
BRCA1 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838905/pdf/Terms of Use
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