Rad51 overexpression rescues radiation resistance in BRCA2-defective cancer cells.
Rad51 overexpression rescues radiation resistance in BRCA2-defective cancer cells.
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DOI：
10.1002/mc.20463
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发表时间：
2009-02
影响因子：
4.6
通讯作者：
Holt, Jeffrey T.
中科院分区：
文献类型：
--
作者：
Brown, Erika T.;Holt, Jeffrey T.
BRCA 2突变的乳腺癌表现出DNA修复缺陷，对辐射特别敏感。BRCA 2以复杂的方式与Rad 51相互作用，涉及内部BRC和C-末端TR 2结构域，它们在同源重组中起关键作用。BRCA 2表达还调节Rad 51蛋白水平，使得Rad 51蛋白在BRCA 2缺陷型癌细胞中相对降低。这部分是通过BRCA 2保护Rad 51免受半胱天冬酶-3蛋白水解降解的能力介导的。为了区分BRCA 2的功能和表达相关作用，我们研究了Rad 51在具有失活BRCA 2突变的小鼠和人类细胞中过表达的结果。结果表明，野生型Rad 51的过表达部分地挽救了BRCA 2缺陷，但是半胱天冬酶-3抗性Rad 51的过表达完全补充了BRCA 2在辐射响应性中的缺陷。这些结果表明，Rad 51可以补偿BRCA 2基因缺陷的某些方面，并表明Rad 51表达水平可能是BRCA 2缺陷基因型的重要修饰剂。
Breast cancers with BRCA2 mutations exhibit DNA repair defects and are particularly sensitive to radiation. BRCA2 interacts with Rad51 in a complex manner involving internal BRC and C-terminal TR2 domains which play a key role in homologous recombination. BRCA2 expression also modulates Rad51 protein levels such that Rad51 protein is relatively decreased in BRCA2-defective cancer cells. This is mediated in part through BRCA2's capacity to protect Rad51 from caspase-3 proteolytic degradation. In order to distinguish between functional and expression related roles for BRCA2 we studied the results of Rad51 overexpression in mouse and human cells with inactivating BRCA2 mutations. The results show that overexpression of wild-type Rad51 partially rescues BRCA2 deficiency but that overexpression of a caspase-3 resistant Rad51 completely complements the BRCA2 defect in radiation responsiveness. These results indicate that Rad51 can compensate for some aspects of a BRCA2 gene defect and suggest that Rad51 expression levels may be an important modifier of the BRCA2 defective genotype.
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影响因子：
30.8
作者：
Connor, F;Bertwistle, D;Ashworth, A
通讯作者：
Ashworth, A
DOI：
10.1093/jnci/90.13.978
发表时间：
1998-07-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Abbott, DW;Freeman, ML;Holt, JT
通讯作者：
Holt, JT
影响因子：
16.8
作者：
Esashi, Fumiko;Galkin, Vitold E.;West, Stephen C.
通讯作者：
West, Stephen C.
影响因子：
16
作者：
Patel, KJ;Yu, VPCC;Venkitaraman, AR
通讯作者：
Venkitaraman, AR
影响因子：
3.4
作者：
Brown, Erika T.;Robinson-Benion, Cheryl;Holt, Jeffrey T.
通讯作者：
Holt, Jeffrey T.