Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif of yeast Msh6
Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif of yeast Msh6
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DOI：
10.1016/j.dnarep.2006.10.023
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发表时间：
2007-03-01
期刊：
影响因子：
3.8
通讯作者：
Kunkel, Thomas A.
中科院分区：
文献类型：
--
作者：
Holmes, Shannon F.;Scarpinato, Karin Drotschmann;Kunkel, Thomas A.
主要的真核错配修复（MMR）途径需要Msh 2-Msh 6，其与大肠杆菌MutS一样，结合并参与修复两种最常见的复制错误，单碱基-碱基错配和单碱基插入-缺失错配。对于这两种类型的错配，E. coliGlu 38中保守的Phe-X-Glu基序与错配碱基相互作用。Glu 38的O键与嘌呤的N7或嘧啶的N3形成氢键。我们在这里表明，改变E。coliGlu 38转化丙氨酸导致单碱基-碱基错配和单碱基缺失错配的修复几乎完全丧失。相比之下，用丙氨酸替换Msh 6中的同源Glu 339的酵母菌株对插入-缺失和大多数碱基-碱基错配具有几乎正常的修复，但在修复氧化应激特征性的碱基-碱基错配（例如8-氧代-G-A错配）方面有缺陷。结果表明，细菌MutS和酵母Msh 2-Msh 6在如何识别和/或处理涉及未受损碱基的复制错误方面存在差异，并且Msh 6中的Glu 339可能在修复含有氧化碱基的错配中发挥专门作用。(c)2006 Elsevier B. V.保留所有权利。
The major eukaryotic mismatch repair (MMR) pathway requires Msh2-Msh6, which, like Escherichia coli MutS, binds to and participates in repair of the two most common replication errors, single base-base and single base insertion-deletion mismatches. For both types of mismatches, the side chain of E. coli Glu38 in a conserved Phe-X-Glu motif interacts with a mismatched base. The O epsilon of Glu38 forms a hydrogen bond with either the N7 of purines or the N3 of pyrimidines. We show here that changing E. coli Glu38 to alanine results in nearly complete loss of repair of both single base-base and single base deletion mismatches. In contrast, a yeast strain with alanine replacing homologous Glu339 in Msh6 has nearly normal repair for insertion-deletion and most base-base mismatches, but is defective in repairing base-base mismatches characteristic of oxidative stress, e.g. 8-oxo-G-A mismatches. The results suggest that bacterial MutS and yeast Msh2-Msh6 differ in how they recognize and/or process replication errors involving undamaged bases, and that Glu339 in Msh6 may have a specialized role in repairing mismatches containing oxidized bases. (c) 2006 Elsevier B.V. All rights reserved.