Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability
Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability
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DOI：
10.1038/sj.onc.1207098
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发表时间：
2004-01-15
期刊：
影响因子：
8
通讯作者：
Jasin, M
中科院分区：
文献类型：
--
作者：
Richardson, C;Stark, JM;Jasin, M
基因组的不稳定性是肿瘤细胞的特征，异常核型与致瘤性之间存在很强的相关性。已报道在永生化细胞和肿瘤细胞中同源重组和DNA修复蛋白Rad51的表达增加，这可能改变重组途径以促成在这些细胞中发现的染色体重排。我们使用了一个遗传系统，以检查潜在的多个双链断裂，导致基因组重排的存在下，Rad51的表达增加。修复分析揭示了一类与交换一致的新型产物，涉及与侧翼标记交换相关的基因转换，导致染色体易位。增加Rad51也促进非整倍体和多染色体重排。这些数据提供了Rad51蛋白水平升高、基因组不稳定性和肿瘤进展之间的联系。
Genomic instability is characteristic of tumor cells, and a strong correlation exists between abnormal karyotype and tumorigenicity. Increased expression of the homologous recombination and DNA repair protein Rad51 has been reported in immortalized and tumor cells, which could alter recombination pathways to contribute to the chromosomal rearrangements found in these cells. We used a genetic system to examine the potential for multiple double-strand breaks to lead to genome rearrangements in the presence of increased Rad51 expression. Analysis of repair revealed a novel class of products consistent with crossing over, involving gene conversion associated with an exchange of flanking markers leading to chromosomal translocations. Increased Rad51 also promoted aneuploidy and multiple chromosomal rearrangements. These data provide a link between elevated Rad51 protein levels, genome instability, and tumor progression.