The BRCA1-Interacting Protein Abraxas Is Required for Genomic Stability and Tumor Suppression

•Abraxas is a haploinsufficient tumor-suppressor gene•Abraxas deficiency causes defective DNA repair and genetic instability•Abraxas-BRCA1 interaction is crucial for DNA repair and genomic stability•Loss of Abraxas function by somatic mutation and gene copy loss in human cancer

SummaryGermline mutations of BRCA1 confer hereditary susceptibility to breast and ovarian cancer. However, somatic mutation of BRCA1 is infrequent in sporadic breast cancers. The BRCA1 protein C terminus (BRCT) domains interact with multiple proteins and are required for BRCA1’s tumor-suppressor function. In this study, we demonstrated that Abraxas, a BRCA1 BRCT domain-interacting protein, plays a role in tumor suppression. Abraxas exerts its function through binding to BRCA1 to regulate DNA repair and maintain genome stability. Both homozygous and heterozygous Abraxas knockout mice exhibited decreased survival and increased tumor incidence. The gene encoding Abraxas suffers from gene copy loss and somatic mutations in multiple human cancers including breast, ovarian, and endometrial cancers, suggesting that mutation and loss of function of Abraxas may contribute to tumor development in human patients.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide