Factors forming the BRCA1-A complex orchestrate BRCA1 recruitment to the sites of DNA damage

Abstract

Sustaining genomic integrity is essential for preventing onset of cancers. Therefore, human cells evolve to have refined biological pathways to defend genetic materials from various genomic insults. DNA damage response and DNA repair pathways essential for genome maintenance are accomplished by cooperative executions of multiple factors including breast cancer type 1 susceptibility protein (BRCA1). BRCA1 is initially identified as an altered gene in the hereditary breast cancer patients. Since then, tremendous efforts to understand the functions of BRAC1 reveal that BRCA1 is found in distinct complexes, including BRCA1-A, BRCA1-B, BRCA1-C, and the BRCA1/ PALB2/BRCA2 complex, and plays diverse roles in a context-dependent manner. Among the complexes, BRCA1-A is critical for BRCA1 recruitment to the sites of DNA damage. Factors comprising the BRCA1-A include RAP80, CCDC98/Abraxas, BRCC36, BRCC45, BARD1, BRCA1, and MERIT40, a RAP80-associated factor. In this review, we summarize recent findings of the factors that form the BRCA1-A complex.

Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population

“…It also has a high MAF in the population databases (0.12 [42] and 0.24 [62]). Together with Abraxas, RAP80 is part of the BRCA1-A complex which is important for recruiting BRCA1 to double-strand break (DSB) sites [63] and studies have shown that truncating variants in both proteins are associated with increased irradiation sensitivity, deficient BRCA1 recruitment to DSB sites and genomic instability [64][65][66][67]. Three patients that carried only these two variants were evaluated for BRCA1/BRCA2 CNVs and all tested negative.…”

RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci

“…Interestingly, the PARsylated region of BRCA1 does not resemble any of the known PAR-containing modules, such as the PBZ, WWE, FHA, OB-fold, RRM, and PIN domains (43), suggesting that it might operate differently, at least in part. In this regard, others have reported that the BRCT domains of the major BRCA1 partner, BARD1, can bind poly-ADP-ribose, which facilitates the early recruitment of BRCA1/BARD1 heterodimers to DSBs (10,40).…”

“…BRCA1 is a major HRR support protein (10,11). Working together with certain partner proteins, including RAD51, CtIP, and BACH1 (also known as FANCJ/BRIP1), it promotes doublestrand break (DSB) end resection, proper HRR progression, and recombinational fidelity (12)(13)(14).…”

Plant Deubiquitinases and Their Role in the Control of Gene Expression Through Modification of Histones

“…BRCA2-CONTAINING COMPLEX 36 HOMOLOG A (BRCC36A) and BRCC36B are two other JAMM proteases in Arabidopsis, which display high sequence similarity to the mammalian BRCC36 that is involved in the DNA damage response pathway as subunit of the BRCA1-A complex, one of the most characterised complex involved in tumour suppression in humans ( Her et al, 2016 ). BRCC36A/B are expressed ubiquitously and neither the single mutants nor the brcc36a/b double mutant shows any developmental problems.…”