title: BRCA2 functions: from DNA repair to replication fork stabilization.
abstract: Maintaining genomic integrity is essential to preserve normal cellular physiology and to prevent the emergence of several human pathologies including cancer. The breast cancer susceptibility gene 2 (BRCA2, also known as the Fanconi anemia (FA) complementation group D1 (FANCD1)) is a potent tumor suppressor that has been extensively studied in DNA double-stranded break (DSB) repair by homologous recombination (HR). However, BRCA2 participates in numerous other processes central to maintaining genome stability, including DNA replication, telomere homeostasis and cell cycle progression. Consequently, inherited mutations in BRCA2 are associated with an increased risk of breast, ovarian and pancreatic cancers. Furthermore, bi-allelic mutations in BRCA2 are linked to FA, a rare chromosome instability syndrome characterized by aplastic anemia in children as well as susceptibility to leukemia and cancer. Here, we discuss the recent developments underlying the functions of BRCA2 in the maintenance of genomic integrity. The current model places BRCA2 as a central regulator of genome stability by repairing DSBs and limiting replication stress. These findings have direct implications for the development of novel anticancer therapeutic approaches.
authors.affiliation: Laval University Cancer Research CenterCHU de Québec Research Center - Université Laval, Hôtel-Dieu de Québec, Oncology Axis, Quebec City, Canada alexandre.orthwein@mcgill.ca Amelie.Fradet-Turcotte@crchudequebec.ulaval.ca.
authors.forename: Amélie
authors.initials: A
authors.lastname: Fradet-Turcotte
authors.affiliation: Laval University Cancer Research CenterCHU de Québec Research Center - Université Laval, Hôtel-Dieu de Québec, Oncology Axis, Quebec City, Canada.
authors.forename: Justine
authors.initials: J
authors.lastname: Sitz
authors.affiliation: Lady Davis Institute for Medical ResearchSegal Cancer Centre, Jewish General Hospital, Montreal, Canada.
authors.forename: Damien
authors.initials: D
authors.lastname: Grapton
authors.affiliation: Lady Davis Institute for Medical ResearchSegal Cancer Centre, Jewish General Hospital, Montreal, Canada Department of OncologyMcGill University, Montreal, Canada alexandre.orthwein@mcgill.ca Amelie.Fradet-Turcotte@crchudequebec.ulaval.ca.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Orthwein
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D018741:Replication Origin / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA2; DNA double-stranded break repair; DNA replication; Fanconi anemia; cancer therapy; genomic stability; homologous recombination; replication stress