Direct visualization of a DNA glycosylase searching for damage

被引:85
作者
Chen, LW [1 ]
Haushalter, KA [1 ]
Lieber, CM [1 ]
Verdine, GL [1 ]
机构
[1] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA
来源
CHEMISTRY & BIOLOGY | 2002年 / 9卷 / 03期
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S1074-5521(02)00120-5
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
DNA glycosylases preserve the integrity of genetic information by recognizing damaged bases in the genome and catalyzing their excision. It is unknown how DNA glycosylases locate covalently modified bases hidden in the DNA helix amongst vast numbers of normal bases. Here we employ atomic-force microscopy (AFM) with carbon nanotube probes to image search intermediates of human 8-oxoguanine DNA glycosylase (hOGG1) scanning DNA. We show that hOGG1 interrogates DNA at undamaged sites by inducing drastic kinks. The sharp DNA bending angle of these non-lesion-specific search intermediates closely matches that observed in the specific complex of 8-oxoguanine-containing DNA bound to hOGG1. These findings indicate that hOGG1 actively distorts DNA while searching for damaged bases.
引用
收藏
页码:345 / 350
页数:6
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