FIGURE 6.

A, the BRCA1-RAP80 complex is recruited to Lys⁶³-linked ubiquitin chains on chromatin surrounding DSBs. Occupancy of BRCA1-RAP80 at DSB chromatin prevents excessive recruitment of the MRN and CtIP nucleases and formation of the BRCA1-CtIP-MRN complex, thereby limiting end resection and maintaining an appropriate balance between HR DSB repair and NHEJ in S and G₂ cell cycle phases. B, BRCA1-RAP80 complex deficiency enables increased access of MRN and CtIP nucleases to chromatin surrounding the DSB. Additionally, in the absence of RAP80, there is a compensatory increase in BRCA1-CtIP-MRN complex formation that may have a minor contribution to excessive end resection. Increased accumulation of MRN and CtIP leads to excessive end resection, with commensurate increases in single-stranded DNA, to favor utilization of HR at the expense of NHEJ in S and G₂ cell cycle phases.