title: The BRCA1-interacting protein Abraxas is required for genomic stability and tumor suppression.
abstract: Germline 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.
authors: Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Andy
authors: A
authors: Castillo
authors: Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Genes and Development Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
authors: Atanu
authors: A
authors: Paul
authors: Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Baohua
authors: B
authors: Sun
authors: Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Genes and Development Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
authors: Ting Hsiang
authors: TH
authors: Huang
authors: Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Yucai
authors: Y
authors: Wang
authors: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
authors: Stephanie A
authors: SA
authors: Yazinski
authors: Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Jessica
authors: J
authors: Tyler
authors: Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Lei
authors: L
authors: Li
authors: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: M James
authors: MJ
authors: You
authors: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
authors: Lee
authors: L
authors: Zou
authors: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Jun
authors: J
authors: Yao
authors: Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Genes and Development Program, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. Electronic address: bwang3@mdanderson.org.
authors: Bin
authors: B
authors: Wang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019313:BRCA1 Protein / Q000737:chemistry / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D005260:Female; D042822:Genomic Instability; D018095:Germ-Line Mutation; D057809:HEK293 Cells; D006720:Homozygote; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: C520310:ABRAXAS1 protein, human; D019313:BRCA1 Protein; D002352:Carrier Proteins; C000600470:FAM175A protein,mouse