title: Elevated radiation-induced γH2AX foci in G2 phase heterozygous BRCA2 fibroblasts.
abstract: OBJECTIVE
  About 5-10% of all breast cancer cases are associated with heterozygous germ-line mutations in the genes encoding BRCA1 and BRCA2. Carriers of such mutations are highly predisposed for developing breast or ovarian cancer and, thus, are advised to undergo regular radio-diagnostic examinations. BRCA1 and BRCA2 are involved in multiple cellular processes including the repair of ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) and different studies addressing the DSB repair capacity of BRCA1+/- or BRCA2+/- cells led to contradictory results.
  
  
  METHODS
  Using the sensitive method of γH2AX foci analysis in combination with cell cycle markers, we specifically measured DSB repair in confluent G0 as well as in exponentially growing G1 and G2 phase primary WT, BRCA1+/- and BRCA2+/- fibroblasts.
  
  
  RESULTS
  Both BRCA1+/- and BRCA2+/- cells displayed normal DSB repair in G0 and in G1. In contrast, in G2, BRCA2+/- but not BRCA1+/- cells exhibited a decreased DSB repair capacity which was in between that of WT and that of a hypomorphic BRCA2-/- cell line.
  
  
  CONCLUSIONS
  The residual amount of normal BRCA1 seems to be sufficient for efficient DSB repair in all cell cycle phases, while the decreased DSB repair capacity of heterozygous BRCA2 mutations suggests gene dosage effects in G2.
authors.affiliation: Radiation Biology and DNA Repair, Darmstadt University of Technology, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Beucher
authors.forename: Dorothee
authors.initials: D
authors.lastname: Deckbar
authors.forename: Eik
authors.initials: E
authors.lastname: Schumann
authors.forename: Andrea
authors.initials: A
authors.lastname: Krempler
authors.forename: Marlis
authors.initials: M
authors.lastname: Frankenberg-Schwager
authors.forename: Markus
authors.initials: M
authors.lastname: Löbrich
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy*; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects*; D016195:G2 Phase / Q000528:radiation effects*; D006579:Heterozygote; D006657:Histones / Q000032:analysis / Q000528:radiation effects*; D006801:Humans; D011829:Radiation Dosage; D011836:Radiation Tolerance; D011839:Radiation, Ionizing
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C468783:H2AX protein, human; D006657:Histones