Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer.
Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer.
复制标题
在结直肠息肉病和癌症患者中发现的 14 种人类 MutY 同源物 (MUTYH) 变异蛋白的腺嘌呤 DNA 糖基化酶活性。
DOI：
10.1002/humu.21363
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发表时间：
2010-11
期刊：
影响因子：
3.9
通讯作者：
Sugimura, Haruhiko
中科院分区：
文献类型：
--
作者：
Goto, Masanori;Shinmura, Kazuya;Nakabeppu, Yusaku;Tao, Hong;Yamada, Hidetaka;Tsuneyoshi, Toshihiro;Sugimura, Haruhiko
关键词：
碱基切除修复MUTYH（MYH）基因中的双等位基因失活种系突变已被证明易患MUTYH相关息肉病（MAP），其特征在于多发性结直肠腺瘤和癌。在这项研究中，我们成功地制备了高度同源的人MUTYH 2型重组蛋白，并比较了野生型蛋白和14种变体蛋白对腺嘌呤与8-羟基鸟嘌呤（鸟嘌呤的氧化形式）错配的DNA糖基化酶活性。p.I195V蛋白、p.G368D蛋白、p.M255V蛋白和p.Y151C蛋白的腺嘌呤DNA糖基化酶活性分别为野生型蛋白的66.9%、15.2%、10.7%和4.5%，而p.R154H、p.L360P、p.P377L、p.452delE、p.R69X、和p.Q310X蛋白以及p.D208N阴性对照形式的表达受到极其严重的损害。另一方面，p.V47E、p.R281C、p.A345V和p.S487F蛋白的糖基化酶活性几乎与野生型蛋白相同。这些结果对于准确诊断MAP和充分理解MUTYH修复腺嘌呤与8-羟基鸟嘌呤错配的DNA的机制具有重要价值。© 2010 Wiley-Liss公司。
Biallelic inactivating germline mutations in the base excision repair MUTYH (MYH) gene have been shown to predispose to MUTYH-associated polyposis (MAP), which is characterized by multiple colorectal adenomas and carcinomas. In this study, we successfully prepared highly homogeneous human MUTYH type 2 recombinant proteins and compared the DNA glycosylase activity of the wild-type protein and fourteen variant-type proteins on adenine mispaired with 8-hydroxyguanine, an oxidized form of guanine. The adenine DNA glycosylase activity of the p.I195V protein, p.G368D protein, p.M255V protein, and p.Y151C protein was 66.9%, 15.2%, 10.7%, and 4.5%, respectively, of that of the wild-type protein, and the glycosylase activity of the p.R154H, p.L360P, p.P377L, p.452delE, p.R69X, and p.Q310X proteins as well as of the p.D208N negative control form was extremely severely impaired. The glycosylase activity of the p.V47E, p.R281C, p.A345V, and p.S487F proteins, on the other hand, was almost the same as that of the wild-type protein. These results should be of great value in accurately diagnosing MAP and in fully understanding the mechanism by which MUTYH repairs DNA in which adenine is mispaired with 8-hydroxyguanine. © 2010 Wiley-Liss, Inc.
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