Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens
Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens
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DOI：
10.1073/pnas.97.14.7927
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发表时间：
2000-07-05
影响因子：
11.1
通讯作者：
Yamaizumi, N
中科院分区：
文献类型：
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作者：
Tateishi, S;Sakuraba, Y;Yamaizumi, N
复制后修复在受损DNA复制时子链的缺口填充中起作用，酵母酿酒酵母Rad 18蛋白与Rad 6蛋白一起在该过程中起关键作用。在此，我们克隆了RAD 18的人类同源物hRAD 18，其定位于染色体3 p24 -25，在肺癌、乳腺癌、卵巢癌和睾丸癌中经常发现该区域的缺失。在体内，hRad 18蛋白通过一个保守的环指基序与hHR 6蛋白结合，hRad 18在该基序中突变的稳定转化子对紫外线、甲磺酸甲酯和丝裂霉素C变得敏感，并且在紫外线损伤的DNA的复制中有缺陷，因此，hRAD 18是RAD 18的功能同源物。
Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA, The yeast Saccharomyces cerevisiae Rad18 protein plays a pivotal role in the process together with the Rad6 protein. Here, we have cloned a human homologue of RAD18, hRAD18, It maps on chromosome 3p24-25, where deletions are often found in lung, breast, ovary, and testis cancers. In vivo, hRad18 protein binds to hHR6 protein through a conserved ring-finger motif, Stable transformants with hRad18 mutated in this motif become sensitive to UV, methyl methanesulfonate, and mitomycin C, and are defective in the replication of UV-damaged DNA, Thus, hRAD18 is a functional homologue of RAD18.