title: The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair.
abstract: Homologous recombinational repair (HRR) of DNA damage is critical for maintaining genome stability and tumor suppression. RAD51 and BRCA2 colocalization in nuclear foci is a hallmark of HRR. BRCA2 has important roles in RAD51 focus formation and HRR of DNA double-strand breaks (DSBs). We previously reported that BCCIPalpha interacts with BRCA2. We show that a second isoform, BCCIPbeta, also interacts with BRCA2 and that this interaction occurs in a region shared by BCCIPalpha and BCCIPbeta. We further show that chromatin-bound BRCA2 colocalizes with BCCIP nuclear foci and that most radiation-induced RAD51 foci colocalize with BCCIP. Reducing BCCIPalpha by 90% or BCCIPbeta by 50% by RNA interference markedly reduces RAD51 and BRCA2 foci and reduces HRR of DSBs by 20- to 100-fold. Similarly, reducing BRCA2 by 50% reduces RAD51 and BCCIP foci. These data indicate that BCCIP is critical for BRCA2- and RAD51-dependent responses to DNA damage and HRR.
authors.affiliation: Department of Molecular Genetics and Microbiology, MSC08-4660, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
authors.forename: Huimei
authors.initials: H
authors.lastname: Lu
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.forename: Xiangbing
authors.initials: X
authors.lastname: Meng
authors.forename: Jingmei
authors.initials: J
authors.lastname: Liu
authors.forename: Chris
authors.initials: C
authors.lastname: Allen
authors.forename: Justin
authors.initials: J
authors.lastname: Wray
authors.forename: Jac A
authors.initials: JA
authors.lastname: Nickoloff
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Shen
mesh_terms: D024682:BRCA2 Protein / Q000032:analysis / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051135:Rad51 Recombinase; D011995:Recombination, Genetic / Q000502:physiology*
chemical_list: C415366:BCCIP protein, human; D024682:BRCA2 Protein; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; C495153:RAD51 protein, human; D051135:Rad51 Recombinase