BRCA1-A and BRISC: Multifunctional Molecular Machines for Ubiquitin Signaling

Abstract

The K63-linkage specific deubiquitinase BRCC36 forms the core of two multi-subunit deubiquitination complexes: BRCA1-A and BRISC. BRCA1-A is recruited to DNA repair foci, edits ubiquitin signals on chromatin, and sequesters BRCA1 away from the site of damage, suppressing homologous recombination by limiting resection. BRISC forms a complex with metabolic enzyme SHMT2 and regulates the immune response, mitosis, and hematopoiesis. Almost two decades of research have revealed how BRCA1-A and BRISC use the same core of subunits to perform very distinct biological tasks.