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PARENT SESSION

Genomic Maintenance & Repair

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP327) Regulation of homologous recombination by BCCIP.

Lu, Huimei*,, Shen, Zhiyuan1, 1 Dept. of Molecular Genetics and Microbiology, MSC08-4660, Albuquerque, NM, USA

ABSTRACT- Homologous recombinational repair (HRR) of DNA damage plays a major role in the maintaining genome stability. BRCA2 has important roles in RAD51 focus formation and HRR of DNA double-strand breaks (DSBs). We previously reported an interaction between BRCA2 and BCCIP, a BRCA2 and CDKN1A (Cip1, p21, Waf1) interacting protein. We have also shown that chromatin-bound BRCA2 co-localizes with BCCIP nuclear foci, and that the majority of radiation-induced RAD51 foci co-localize with BCCIP. In this study, we further show that dominant negative BCCIP fragments reduce DSB-induced HRR. Interestingly, both the BRCA2 and p21 interacting domains of BCCIP inhibit DSB-induced HRR, implying that both the BRCA2-BCCIP and p21-BCCIP interaction may be important for homologous recombination. Furthermore, knockdown of BCCIP expression by RNA interference inhibits homology based gene targeting in human cells. These results affirm the role of BCCIP in HRR regulation.

Key words: homologous recombination, BRCA2, BCCIP, DSB repair


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2005 RRS