The BRCA1-RAP80 complex regulates DNA repair mechanism utilization by restricting end resection.

The tumor suppressor protein BRCA1 is a constituent of several different protein complexes and is required for homology-directed repair (HDR) of DNA double strand breaks (DSBs). The most recently discovered BRCA1-RAP80 complex is recruited to ubiquitin structures on chromatin surrounding the break. Deficiency of any member of this complex confers ...
hypersensitivity to DNA-damaging agents by undefined mechanisms. In striking contrast to other BRCA1-containing complexes that are known to promote HDR, we demonstrate that the BRCA1-RAP80 complex restricts end resection in S/G(2) phase of the cell cycle, thereby limiting HDR. RAP80 or BRCC36 deficiency resulted in elevated Mre11-CtIP-dependent 5' end resection with a concomitant increase in HDR mechanisms that rely on 3' single-stranded overhangs. We propose a model in which the BRCA1-RAP80 complex limits nuclease accessibility to DSBs, thus preventing excessive end resection and potentially deleterious homology-directed DSB repair mechanisms that can impair genome integrity.
Mesh Terms:
BRCA1 Protein, Carrier Proteins, Chromatin, DNA Breaks, Double-Stranded, DNA Repair, DNA-Binding Proteins, G2 Phase, Genomic Instability, HeLa Cells, Humans, Membrane Proteins, Multiprotein Complexes, Nuclear Proteins, S Phase
J. Biol. Chem.
Date: Apr. 15, 2011
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