The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair
The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair
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DOI：
10.1128/mcb.25.5.1949-1957.2005
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发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Shen, ZY
中科院分区：
文献类型：
--
作者：
Lu, HM;Guo, X;Shen, ZY
DNA损伤的同源重组修复（HRR）对于维持基因组稳定性和肿瘤抑制至关重要。RAD 51和BRCA 2共定位于核灶中是HRR的标志。BRCA 2在RAD 51病灶形成和DNA双链断裂（DSB）的HRR中起重要作用。我们以前报道过13 CCIPalpha与BRCA 2相互作用。我们发现，第二个亚型，BCCIPP，也与BRCA 2相互作用，这种相互作用发生在一个区域共享的BCCIPot和BCCIPP。我们进一步表明，染色质结合BRCA 2与BCCIP核病灶共定位，大多数辐射诱导的RAD 51病灶与BCCIP共定位。通过RNA干扰将BCCIPalpha降低90%或BCCIPbeta降低50%显著降低了RAD 51和BRCA 2病灶，并将DSB的HRR降低了20- 100倍。类似地，将BRCA 2降低50%会降低RAD 51和BCCIP病灶。这些数据表明，BCCIP对于BRCA 2和RAD 51依赖性的DNA损伤和HRR反应至关重要。
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 13CCIPalpha interacts with BRCA2. We show that a second isoform, BCCIPP, also interacts with BRCA2 and that this interaction occurs in a region shared by BCCIPot and BCCIPP. 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.