Recombination Activator Function of the Novel RAD51-and RAD51B-binding Protein, Human EVL
Recombination Activator Function of the Novel RAD51-and RAD51B-binding Protein, Human EVL
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DOI：
10.1074/jbc.m807715200
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发表时间：
2009-05-22
影响因子：
4.8
通讯作者：
Kurumizaka, Hitoshi
中科院分区：
文献类型：
--
作者：
Takaku, Motoki;Machida, Shinichi;Kurumizaka, Hitoshi
RAD51蛋白在同源重组修复中起核心作用。RAD51B蛋白是高等真核生物中在同源重组修复途径中发挥作用的五个RAD51类似物之一。在本研究中，我们发现可能参与肌动蛋白重塑过程的人EVL(Ena/Vasp-like)蛋白意外地与RAD51和RAD51B蛋白结合，并刺激RAD51介导的同源配对和链交换。EVL基因敲除细胞在电离辐射或丝裂霉素C处理后，破坏了RAD51在受损DNA上的组装。EVL蛋白单独促进单链DNA退火，RAD51B蛋白进一步增强EVL蛋白的重组活性。EVL蛋白的表达并不普遍，但它在乳腺癌来源的MCF7细胞中显著表达。这些结果表明，EVL蛋白是一种新的重组因子，可能是修复特定DNA损伤所必需的，并可能通过其不适当的表达而导致肿瘤恶性。
The RAD51 protein is a central player in homologous recombinational repair. The RAD51B protein is one of five RAD51 paralogs that function in the homologous recombinational repair pathway in higher eukaryotes. In the present study, we found that the human EVL (Ena/Vasp-like) protein, which is suggested to be involved in actin-remodeling processes, unexpectedly binds to the RAD51 and RAD51B proteins and stimulates the RAD51-mediated homologous pairing and strand exchange. The EVL knockdown cells impaired RAD51 assembly onto damaged DNA after ionizing radiation or mitomycin C treatment. The EVL protein alone promotes single-stranded DNA annealing, and the recombination activities of the EVL protein are further enhanced by the RAD51B protein. The expression of the EVL protein is not ubiquitous, but it is significantly expressed in breast cancer-derived MCF7 cells. These results suggest that the EVL protein is a novel recombination factor that may be required for repairing specific DNA lesions, and that may cause tumor malignancy by its inappropriate expression.