title: Unsolved mystery: the role of BRCA1 in DNA end-joining.
abstract: Heritable mutations in the tumor suppressor gene BRCA1 increase a woman's lifetime risk of developing breast and ovarian cancer. BRCA1's tumor suppressor function is directly linked to its myriad of functions in the cellular response to DNA double-strand breaks (DSBs). BRCA1 interacts with an extensive array of DNA damage responsive proteins and plays important roles in DSB repair, mediated by the homologous recombination pathway, and in the activation of cell cycle checkpoints. However, the role of BRCA1 in the other two DSB repair pathways, classical non-homologous end-joining (C-NHEJ) and alternative NHEJ (A-NHEJ), remains unclear. In this review, we will discuss the current literature on BRCA1's potential role(s) in modulating both C-NHEJ and A-NHEJ. We also present a model showing that BRCA1 contributes to genomic maintenance by promoting precise DNA repair across all cell cycle phases via the direct modulation of DNA end-joining.
authors.affiliation: Department of Radiation Oncology, Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center, 2201 Inwood Rd, Dallas, Texas 75390-9187, USA.
authors.forename: Janapriya
authors.initials: J
authors.lastname: Saha
authors.affiliation: Department of Radiation Oncology, Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center, 2201 Inwood Rd, Dallas, Texas 75390-9187, USA anthony.davis@utsouthwestern.edu.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D005260:Female; D006801:Humans; D008954:Models, Biological
chemical_list: D019313:BRCA1 Protein
keywords: BRCA1; DNA-PKcs; HR; Ku70/80; NHEJ; breast cancer