Lys-63-specific deubiquitinase BRCC36 (BRCC3)

Lys-63-specific deubiquitinase BRCC36 (BRCC3) is a zinc metalloprotease and a member of the JAMM/MPN+ family, functioning as a deubiquitinase that specifically cleaves Lys63-linked polyubiquitin chains[1][2][3][4][6]. As a core subunit of the BRCA1-A and BRISC complexes, it is pivotal in the cellular DNA damage response, supporting stable accumulation and regulation of BRCA1 at double-strand DNA breaks and promoting DNA repair via homologous recombination[1][3][4]. BRCC3 also modulates cell cycle checkpoint signaling, inflammasome activity, and angiogenesis[2][4]. Mutations or loss of function are implicated in myeloid neoplasms, resistance to DNA-damaging therapies, and rare vascular developmental disorders such as moyamoya disease[1][2][6]. BRCC3 interacts with BRCA1, BRCA2, RAD51, P53, and BARD1, highlighting its central role in maintaining genomic stability[3][4].

Other names

BRCA1/BRCA2-containing complex subunit 3BRCC36C6.1ACXorf53BRCA1-A complex subunit BRCC36BRISC complex subunit BRCC36

Inhibition or knockdown of BRCC3 increases sensitivity to DNA-damaging agents (e.g., temozolomide)[4]; general mechanisms would be inhibition of deubiquitinase activity leading to impaired DNA repair, increased DNA damage, and apoptosis