Figure 1.

Effects of BRCA1 RING and BRCT domain mutations on homologous recombination. (A) The BRCA1 protein consists of an N-terminal RING domain possessing E3 ubiquitin-ligase activity and two tandem C-terminal BRCT repeats that bind phosphoproteins such as Abraxas-RAP80 (BRCA1-A complex). (B) Mutations in the RING domain that disrupt the ubiquitin-ligase activity of BRCA1, but not BARD1 binding, do not affect HR.¹¹,²⁶ (C) Certain mutations in the BRCT binding pocket that disrupt interactions with phosphoproteins, or silencing of the BRCA1 A complex, results in aberrant, hyper-HR (HHR).²⁴–²⁶ (D) Mutations in both the RING and BRCT domains diminish HHR, suggesting a dependence of ubiquitinylation specifically in HHR but not in HR.²⁶ ↑, increase; ↓, decrease; ↔, no change; ?, unknown; *, no effect²⁴,²⁶ or decreased²⁵ NHEJ.