Together with the breast and ovarian predisposition proteins BRCA1 and BRCA2 and RAD51 and BRCC45, BRCC36 forms a holoenzyme complex that possesses a ubiquitin E3 ligase activity. Aberrant levels of BRCC36 were detected in sporadic breast tumors and depletion of either BRCC36 or BRCC45 by siRNA resulted in increased sensitivity to ionizing radiation and defects in the G2/M checkpoint, indicating that BRCC36 acts to enhance cellular survival following DNA damage. Recent experiments have shown that BRCC36 is essential for ionizing radiation-induced BRCA1 phosphorylation and nuclear foci formation, suggesting that BRCC36 may be an important target in the treatment of radiation-resistant breast tumors. At least two isoforms of BRCC36 are known to exist.