Cellular functions of the BRCA tumour-suppressor proteins

摘要: Inherited germline mutations in either BRCA1 or BRCA2 confer a significant lifetime risk of developing breast ovarian cancer. Defining how these two genes function at the cellular level is essential for understanding their role tumour suppression. Although and were independently cloned over 10 years ago, it only last few years that progress has been made towards cells. It now widely accepted both play critical roles maintenance genome stability. Evidence implicates as an integral component homologous recombination machinery, whereas E3 ubiquitin ligase impact on DNA repair, transcriptional regulation, cell-cycle progression meiotic sex chromosome inactivation. In this article, I will review most recent advances provide perspective potential future directions field. Abbreviations: ATM, ataxia telangiectasia mutated; ATR, ATM- Rad3-related; BAP, BRCA1-associated protein; BARD1, RING domain 1; BRCT, C-terminus; BRIP, BRCA1-interacting Cdk, cyclin-dependent kinase; CtIP, C-terminal-binding-protein-interacting DSB, double-strand break; dsDNA, double-stranded DNA; FA, Fanconi's anaemia; FANC, FA complementation group; GST, glutathione S-transferase; HR, recombination; MRN, Mre11–Rad50–Nbs1; MSCI, inactivation; NHEJ, non-homologous end joining; OB, oligonucleotide/oligosaccharide-binding; SCF, Skp1/cullin/F-box; siRNA, small interfering RNA; SSA, single-strand annealing; ssDNA, single-stranded Ub, ubiquitin; Xi, inactive X chromosome; XIST, Xi-specific transcript