A role for RAD54B in homologous recombination in human cells
A role for RAD54B in homologous recombination in human cells
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DOI：
10.1093/emboj/21.1.175
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发表时间：
2002-01-15
期刊：
影响因子：
11.4
通讯作者：
Tanaka, K
中科院分区：
文献类型：
--
作者：
Miyagawa, K;Tsuruga, T;Tanaka, K
在人类体细胞中，同源重组是一种罕见的事件。为了促进基因组的靶向修饰研究和基因治疗应用，应该努力了解人类细胞中同源重组的分子机制。虽然已经鉴定出与酵母菌RAD52上位群成员同源的人类基因，但没有基因被证明在人类细胞的同源重组中起作用。在这里，我们报道RAD54B在人类细胞的靶向整合中起关键作用。RAD54B在结肠癌细胞系中的失活导致靶向整合频率严重降低。rad54b缺陷细胞对dna损伤剂和姊妹染色单体交换的敏感性不受影响。这些表型部分与酿酒酵母tid1/rdh54突变体相似，提示RAD54B可能是tid1/rdh54的人类同源物。在酵母中，TID1/RDH54通过部分重叠RAD54的作用参与重组修复途径。我们的发现提供了第一个遗传证据，证明有丝分裂重组途径在功能上从酵母到人类是保守的。
In human somatic cells, homologous recombination is a rare event. To facilitate the targeted modification of the genome for research and gene therapy applications, efforts should be directed toward understanding the molecular mechanisms of homologous recombination in human cells. Although human genes homologous to members of the RAD52 epistasis group in yeast have been identified, no genes have been demonstrated to play a role in homologous recombination in human cells. Here, we report that RAD54B plays a critical role in targeted integration in human cells. Inactivation of RAD54B in a colon cancer cell line resulted in severe reduction of targeted integration frequency. Sensitivity to DNA-damaging agents and sister-chromatid exchange were not affected in RAD54B-deficient cells. Parts of these phenotypes were similar to those of Saccharomyces cerevisiae tid1/rdh54 mutants, suggesting that RAD54B may be a human homolog of TID1/RDH54. In yeast, TID1/RDH54 acts in the recombinational repair pathway via roles partially overlapping those of RAD54. Our findings provide the first genetic evidence that the mitotic recombination pathway is functionally conserved from yeast to humans.