title: Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining.
abstract: Carriers of BRCA2 germline mutations are at high risk to develop early-onset breast cancer. The underlying mechanisms of how BRCA2 inactivation predisposes to malignant transformation have not been established. Here, we provide direct functional evidence that human BRCA2 promotes homologous recombination (HR), which comprises one major pathway of DNA double-strand break repair. We found that up-regulated HR after transfection of wild-type (wt) BRCA2 into a human tumor line with mutant BRCA2 was linked to increased radioresistance. In addition, BRCA2-mediated enhancement of HR depended on the interaction with Rad51. In contrast to the tumor suppressor BRCA1, which is involved in multiple DNA repair pathways, BRCA2 status had no impact on the other principal double-strand break repair pathway, nonhomologous end joining. Thus, there exists a specific regulation of HR by BRCA2, which may function to maintain genomic integrity and suppress tumor development in proliferating cells.
authors.affiliation: Laboratory of Molecular and Cellular Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: F
authors.initials: F
authors.lastname: Xia
authors.forename: D G
authors.initials: DG
authors.lastname: Taghian
authors.forename: J S
authors.initials: JS
authors.lastname: DeFrank
authors.forename: Z C
authors.initials: ZC
authors.lastname: Zeng
authors.forename: H
authors.initials: H
authors.lastname: Willers
authors.forename: G
authors.initials: G
authors.lastname: Iliakis
authors.forename: S N
authors.initials: SN
authors.lastname: Powell
mesh_terms: D024682:BRCA2 Protein; D003434:Crossing Over, Genetic; D005260:Female; D005785:Gene Conversion; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors