Structure of a trapped endonuclease III-DNA covalent intermediate

被引：168

作者：

Fromme, JC

Verdine, GL ^{[1
]}

机构：

[1] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[2] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA

来源：

EMBO JOURNAL | 2003年 / 22卷 / 13期

关键词：

crystal structure; DNA glycosylase; DNA repair; endonuclease III; 4Fe-4S] cluster;

D O I：

10.1093/emboj/cdg311

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：

Nearly all cells express proteins that confer resistance to the mutagenic effects of oxidative DNA damage. The primary defense against the toxicity of oxidative nucleobase lesions in DNA is the base-excision repair (BER) pathway. Endonuclease III (EndoIII) is a [4Fe-4S] cluster-containing DNA glycosylase with repair activity specific for oxidized pyrimidine lesions in duplex DNA. We have determined the crystal structure of a trapped intermediate that represents EndoIII frozen in the act of repairing DNA. The structure of the protein-DNA complex provides insight into the ability of EndoIII to recognize and repair a diverse array of oxidatively damaged bases. This structure also suggests a rationale for the frequent occurrence in certain human cancers of a specific mutation in the related DNA repair protein MYH.

引用

页码：3461 / 3471

页数：11

共 72 条

[71] NH2-terminal proline acts as a nucleophile in the glycosylase/AP-lyase reaction catalyzed by Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg) protein [J].