BRCA2 has an essential role in DNA repair, and therefore primary cells exhibit severe proliferation defect or fail to survive in its absence. Yet, BRCA2-deficiency results in tumorigenesis. It is believed that mutations in genes like TP53 contribute to the viability of BRCA2-deficient cells that subsequently undergo neoplastic transformation due to their unstable genome. To identify other genes that contribute to cell survival in the absence of BRCA2, we have undertaken an insertional mutagenesis screen using the Murine Stem Cell Virus (MSCV). Here we describe one of the genes identified in the screen, brain and reproductive organ expressed (TNFRSF1A modulator) (BRE), also known as BRCC45. BRE is a component of the BRCA1-complex that specifically recognizes the Lys-63-linked ubiquitinated histones H2A and H2AX at the site of DNA damage. We found that overexpression of BRE can rescue the lethality of Brca2 null mES cells. Furthermore, our findings revealed that its overexpression results in perturbation of DNA damage induced degradation of CDC25A phosphatase, a key cell cycle regulator and an oncogene, by facilitating deubiquitylation through ubiquitin specific peptidase 7 (USP7). The oncogenic role of BRE is demonstrated by its effect on the growth of BRCA2-deficient tumor cells in mice and the positive correlation between BRE overexpression and CDC25A levels is confirmed in human breast tumors. Altogether, our findings demonstrate a novel oncogenic role for BRE that is independent of its known role in BRCA1-mediated tumor suppression.