Identification of a novel human Rad51 variant that promotes DNA strand exchange.

Identification of a novel human Rad51 variant that promotes DNA strand exchange.
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DOI:
10.1093/nar/gkn171
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发表时间:
2008-06
影响因子:
14.9
通讯作者:
Kim, Youngho
Kim, Youngho
中科院分区:
生物学2区
文献类型:
--
作者:
Park, Jung-Young;Yoo, Han-Wook;Kim, Bok-Ryang;Park, Raekil;Choi, Sang-Yun;Kim, Youngho

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Rad51 在通过同源重组修复 DNA 双链断裂中发挥着关键作用,这是维持基因组完整性的核心过程。迄今为止,已鉴定出人类 Rad51 基因 (hRad51) 的五个旁系同源物,包括 hRad51B、hRad51C、hRad51D、Xrcc2 和 Xrcc3。在搜索其他 hRad51 旁系同源物时,我们发现了一种新的 hRad51 变体,它缺少与外显子 9 相对应的序列 (hRad51-Δex9)。 hRad51-Δex9 的预期氨基酸序列在密码子 259 处显示移码,导致 C 末端截短。 RT-PCR分析显示hRad51和hRad51-Δex9均在睾丸中显着表达,但组织特异性存在细微差异。 hRad51-Δex9 蛋白在睾丸中被检测为 31 kDa 蛋白,且定位于细胞核。此外,hRad51-Δex9蛋白显示出与hRad51相当的DNA链交换活性。总而言之,这些结果表明 hRad51-Δex9 促进细胞核中的同源配对和 DNA 链交换,这表明存在 hRad51 或 hRad51-Δex9 依赖方式的替代途径用于 DNA 重组和修复。
Rad51 plays a key role in the repair of DNA double-strand breaks through homologous recombination, which is the central process in the maintenance of genomic integrity. Five paralogs of the human Rad51 gene (hRad51) have been identified to date, including hRad51B, hRad51C, hRad51D, Xrcc2 and Xrcc3. In searches of additional hRad51 paralogs, we identified a novel hRad51 variant that lacked the sequence corresponding to exon 9 (hRad51-Δex9). The expected amino acid sequence of hRad51-Δex9 showed a frame-shift at codon 259, which resulted in a truncated C-terminus. RT-PCR analysis revealed that both hRad51 and hRad51-Δex9 were prominently expressed in the testis, but that there were subtle differences in tissue specificity. The hRad51-Δex9 protein was detected as a 31-kDa protein in the testis and localized at the nucleus. In addition, the hRad51-Δex9 protein showed a DNA-strand exchange activity comparable to that of hRad51. Taken together, these results indicate that hRad51-Δex9 promotes homologous pairing and DNA strand exchange in the nucleus, suggesting that alternative pathways in hRad51- or hRad51-Δex9-dependent manners exist for DNA recombination and repair.
DOI: 10.1093/mutage/gei011
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期刊: MUTAGENESIS
影响因子: 2.7
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发表时间: 2003-12-26
影响因子: 4.8
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发表时间: 1999-12-23
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