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Molecular and Cellular Biology, March 2005, p. 1949-1957, Vol. 25, No. 5
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.5.1949-1957.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair
Huimei Lu,1
Xu Guo,
Xiangbing Meng,
Jingmei Liu,
Chris Allen,
Justin Wray,
Jac A. Nickoloff, and
Zhiyuan Shen*
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico
Received 17 August 2004/
Returned for modification 13 September 2004/
Accepted 29 November 2004
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 BCCIP
interacts with BRCA2. We show that a second isoform, BCCIPß, also interacts with BRCA2 and that this interaction occurs in a region shared by BCCIP
and BCCIPß. We further show that chromatin-bound BRCA2 colocalizes with BCCIP nuclear foci and that most radiation-induced RAD51 foci colocalize with BCCIP. Reducing BCCIP
by 90% or BCCIPß 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.
* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, MSC08-4660, University of New Mexico School of Medicine, Albuquerque, NM 87131. Phone: (505) 272-4291. Fax: (505) 272-6029. E-mail:
zshen{at}salud.unm.edu.
Present address: Department of Medicine, University of Florida, Gainesville, FL 32610-0226.
Present address: Department of Biology, University of New Mexico, Albuquerque, NM 87131.
Molecular and Cellular Biology, March 2005, p. 1949-1957, Vol. 25, No. 5
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.5.1949-1957.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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