title: BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability.
abstract: BRCA1 plays a critical role in the regulation of homologous recombination (HR)-mediated DNA double-strand break repair. BRCA1-deficient cancers have evolved to tolerate loss of BRCA1 function. This renders them vulnerable to agents, such as PARP inhibitors, that are conditionally 'synthetic lethal' with their underlying repair defect. Recent studies demonstrate that BRCA1-deficient cells may acquire resistance to these agents by partially correcting their defect in HR-mediated repair, either through reversion mutations in BRCA1 or through 'synthetic viable' loss of 53BP1. These findings and their clinical implications will be reviewed in this article.
authors.affiliation: Cancer Institute of New Jersey, Robert Wood Johnson Medical School-UMDNJ, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
authors.forename: Amal
authors.initials: A
authors.lastname: Aly
authors.forename: Shridar
authors.initials: S
authors.lastname: Ganesan
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D005804:Genes, Lethal / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D019313:BRCA1 Protein; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D011065:Poly(ADP-ribose) Polymerases