Excision of 8-oxoguanine from methylated CpG dinucleotides by human 8-oxoguanine DNA glycosylase

被引：18
|
作者：
Kasymov, Rustem D. [1 ]
Grin, Inga R. [1 ,2 ]
Endutkin, Anton V. [1 ]
Smirnov, Serge L. [3 ]
Ishchenko, Alexander A. [2 ]
Saparbaev, Murat K. [2 ]
Zharkov, Dmitry O. [1 ,4 ]
机构：
[1] SB RAS Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia
[2] Univ Paris 11, Inst Cancerol Gustave Roussy, CNRS UMR8200, Grp Reparat ADN, Villejuif, France
[3] Western Washington Univ, Dept Chem, Bellingham, WA 98225 USA
[4] Novosibirsk State Univ, Fac Nat Sci, Dept Mol Biol, Novosibirsk 630090, Russia
来源：
FEBS LETTERS | 2013年 / 587卷 / 18期
基金：
俄罗斯基础研究基金会;
关键词：
DNA repair; Epigenetic methylation; 5-Methylcytosine; 8-Oxoguanine; OGG1; AP LYASE ACTIVITY; SUBSTRATE-SPECIFICITY; POLYMORPHIC VARIANT; REPAIR; PROTEIN; ENDONUCLEASE; STIMULATION; RECOGNITION; MECHANISM; PRODUCT;
D O I：
10.1016/j.febslet.2013.08.008
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
CpG dinucleotides are targets for epigenetic methylation, many of them bearing 5-methylcytosine (mCyt) in the human genome. Guanine in this context can be easily oxidized to 8-oxoguanine (oxoGua), which is repaired by 8-oxoguanine-DNA glycosylase (OGG1). We have studied how methylation affects the efficiency of oxoGua excision from damaged CpG dinucleotides. Methylation of the adjacent cytosine moderately decreased the oxoGua excision rate while methylation opposite oxoGua lowered the rate of product release. Cytosine methylation abolished stimulation of OGG1 by repair endonuclease APEX1. The OGG1 S326C polymorphic variant associated with lung cancer showed poorer base excision and lost sensitivity to the opposite-base methylation. The overall repair in the system reconstituted from purified proteins decreased for CpG with mCyt in the damaged strand. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码：3129 / 3134
页数：6
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