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Rad51蛋白的过表达刺激同源重组并增加哺乳动物细胞对电离辐射的抗性。

Overexpression of Rad51 protein stimulates homologous recombination and increases resistance of mammalian cells to ionizing radiation.

作者信息

Vispé S, Cazaux C, Lesca C, Defais M

机构信息

Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, UPR 9062, 205 route de Narbonne, 31077 Toulouse cédex, France.

出版信息

Nucleic Acids Res. 1998 Jun 15;26(12):2859-64. doi: 10.1093/nar/26.12.2859.

Abstract

Rad51 proteins share both structural and functional homologies with the bacterial recombinase RecA. The human Rad51 (HsRad51) is able to catalyse strand exchange between homologous DNA molecules in vitro . However the biological functions of Rad51 in mammals are largely unknown. In order to address this question, we have cloned hamster Rad51 cDNA and overexpressed the corresponding protein in CHO cells. We found that 2-3-fold overexpression of the protein stimulated the homologous recombination between integrated genes by 20-fold indicating that Rad51 is a functional and key enzyme of an intrachromosomal recombination pathway. Cells overexpressing Rad51 were resistant to ionizing radiation when irradiated in late S/G2phase of the cell cycle. This suggests that Rad51 participate in the repair of double-strand breaks most likely by homologous recombination involving sister chromatids formed after the S phase.

摘要

Rad51蛋白与细菌重组酶RecA在结构和功能上都具有同源性。人类Rad51(HsRad51)能够在体外催化同源DNA分子之间的链交换。然而,Rad51在哺乳动物中的生物学功能在很大程度上尚不清楚。为了解决这个问题,我们克隆了仓鼠Rad51 cDNA,并在CHO细胞中过表达了相应的蛋白。我们发现该蛋白2至3倍的过表达使整合基因之间的同源重组增强了20倍,这表明Rad51是染色体内部重组途径的一种功能性关键酶。在细胞周期的S/G2晚期进行照射时,过表达Rad51的细胞对电离辐射具有抗性。这表明Rad51很可能通过涉及S期后形成的姐妹染色单体的同源重组参与双链断裂的修复。

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Double-strand break-induced recombination in eukaryotes.真核生物中双链断裂诱导的重组
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