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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,{dagger} Xiangbing Meng, Jingmei Liu, Chris Allen,{ddagger} 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{alpha} 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{alpha} 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{alpha} 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.

{dagger} Present address: Department of Medicine, University of Florida, Gainesville, FL 32610-0226.

{ddagger} 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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