The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair |
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| Authors: | Lu Huimei Guo Xu Meng Xiangbing Liu Jingmei Allen Chris Wray Justin Nickoloff Jac A Shen Zhiyuan |
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| Affiliation: | Department of Molecular Genetics and Microbiology, MSC08-4660, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. |
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| 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. |
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