Mutagenic conformation of 8-oxo-7,8-dihydro-2′-dGTP in the confines of a DNA polymerase active site

被引:49
作者
Batra, Vinod K. [1 ]
Beard, William A. [1 ]
Hou, Esther W. [1 ]
Pedersen, Lars C. [1 ]
Prasad, Rajendra [1 ]
Wilson, Samuel H. [1 ]
机构
[1] Natl Inst Environm Hlth Sci, Struct Biol Lab, US Natl Inst Hlth, Res Triangle Pk, NC 27709 USA
基金
美国国家卫生研究院;
关键词
STRUCTURAL INSIGHTS; BETA; FIDELITY; MECHANISM; LESION; MISINCORPORATION; DUPLEX;
D O I
10.1038/nsmb.1852
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
The major product of oxidative base damage is 8-oxo-7,8-dihydro-2'-deoxyguanine (8odG). The coding potential of this lesion is modulated by its glycosidic torsion angle that controls whether its Watson-Crick or Hoogsteen edge is used for base pairing. The 2.0-angstrom structure of DNA polymerase (pol) beta bound with 8odGTP opposite template adenine indicates that the modified nucleotide assumes the mutagenic syn conformation and that the nonmutagenic anti conformation would be incompatible with efficient DNA synthesis.
引用
收藏
页码:889 / 890
页数:2
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