title: Analysis of murine Brca2 reveals conservation of protein-protein interactions but differences in nuclear localization signals.
abstract: In this report, we have analyzed the protein encoded by the murine Brca2 locus. We find that murine Brca2 shares multiple properties with human BRCA2 including its regulation during the cell cycle, localization to nuclear foci, and interaction with Brca1 and Rad51. Murine Brca2 stably interacts with human BRCA1, and the amino terminus of Brca2 is sufficient for this interaction. Exon 11 of murine Brca2 is required for its stable association with RAD51, whereas the carboxyl terminus of Brca2 is dispensable for this interaction. Finally, in contrast to human BRCA2, we demonstrate that carboxyl-terminal truncations of murine Brca2 localize to the nucleus. This finding may explain the apparent inconsistency between the cytoplasmic localization of carboxyl-terminal truncations of human BRCA2 and the hypomorphic phenotype of mice homozygous for similar carboxyl-terminal truncating mutations.
authors.affiliation: Department of Molecular and Cellular Engineering, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Sarkisian
authors.forename: S R
authors.initials: SR
authors.lastname: Master
authors.forename: L J
authors.initials: LJ
authors.lastname: Huber
authors.forename: S I
authors.initials: SI
authors.lastname: Ha
authors.forename: L A
authors.initials: LA
authors.lastname: Chodosh
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D024682:BRCA2 Protein / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005091:Exons; D016195:G2 Phase / Q000502:physiology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D008938:Mitosis / Q000502:physiology; D017434:Protein Structure, Tertiary; D051135:Rad51 Recombinase; D016196:S Phase / Q000502:physiology; D015854:Up-Regulation
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004268:DNA-Binding Proteins; D007106:Immune Sera; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse