The human Rad54 recombinational DNA repair protein is a double-stranded DNA-dependent ATPase
The human Rad54 recombinational DNA repair protein is a double-stranded DNA-dependent ATPase
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DOI：
10.1074/jbc.273.43.28292
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发表时间：
1998-10-23
影响因子：
4.8
通讯作者：
Kanaar, R
中科院分区：
文献类型：
--
作者：
Swagemakers, SMA;Essers, J;Kanaar, R
在酵母酿酒酵母中通过RAD 52同源重组途径的DNA双链断裂修复需要RAD 51、RAD 52和RAD 54基因等。同源重组的生物学重要性通过从真菌到人类的RAD52途径的保守性来强调。RAD52组蛋白在重组的早期步骤，寻找DNA同源性和链交换中的关键作用现在变得越来越明显。在这里，我们报告了人Rad54蛋白的纯化。我们发现，人Rad54具有绝对依赖于双链DNA的ATP酶活性。出乎意料的是，ATP酶活性似乎不是人Rad54体内DNA修复功能所绝对需要的。尽管存在在DNA解旋酶的大家族中保守的氨基酸序列基序，但在各种不同的DNA底物上没有观察到人Rad54的解旋酶活性。人类Rad54在同源重组中可能的功能，耦合从ATP水解获得的能量沿着DNA易位，而不是破坏碱基配对，进行了讨论。
DNA double-strand break repair through the RAD52 homologous recombination pathway in the yeast Saccharomyces cerevisiae requires, among others, the RAD51, RAD52, and RAD54 genes. The biological importance of homologous recombination is underscored by the conservation of the RAD52 pathway from fungi to humans. The critical roles of the RAD52 group proteins in the early steps of recombination, the search for DNA homology and strand exchange, are now becoming apparent. Here, we report the purification of the human Rad54 protein. We showed that human Rad54 has ATPase activity that is absolutely dependent on double-stranded DNA. Unexpectedly, the ATPase activity appeared not absolutely required for the DNA repair function of human Rad54 in vivo. Despite the presence of amino acid sequence motifs that are conserved in a large family of DNA helicases, no helicase activity of human Rad54 was observed on a variety of different DNA substrates. Possible functions of human Rad54 in homologous recombination that couple the energy gained from ATP hydrolysis to translocation along DNA, rather than disruption of base pairing, are discussed.