Lesion processing: high-fidelity versus lesion-bypass DNA polymerases

被引：55

作者：

Broyde, Suse ^{[1
]}

Wang, Lihua ^{[1
]}

Rechkoblit, Olga ^{[2
]}

Geacintov, Nicholas E. ^{[3
]}

Patel, Dinshaw J. ^{[2
]}

机构：

[1] NYU, Dept Biol, New York, NY 10003 USA

[2] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA

[3] NYU, Dept Chem, New York, NY 10003 USA

来源：

TRENDS IN BIOCHEMICAL SCIENCES | 2008年 / 33卷 / 05期

关键词：

D O I：

10.1016/j.tibs.2008.02.004

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：

When a high-fidelity DNA polymerase encounters certain DNA-damage sites, its progress can be stalled and one or more lesion-bypass polymerases are recruited to transit the lesion. Here, we consider two representative types of lesions: (i) 7,8-dihydro-8-oxoguanine (8-oxoG), a small, highly prevalent lesion caused by Oxidative damage; and (ii) bulky lesions derived from the environmental pre-carcinogen benzo[a]pyrene, in the high-fidelity DNA polymerase Bacillus fragment (BF) from Bacillus stearothermophilus and in the lesion-bypass DNA polymerase IV (Dpo4) from Sulfolobus solfataricus. The tight fit of the BF polymerase around the nascent base pair contrasts with the more spacious, solvent-exposed active site of Dpo4, and these differences in architecture result in distinctions in their respective functions: one-step versus stepwise polymerase translocation, mutagenic versus accurate bypass of 8-oxoG, and polymerase stalling versus mutagenic bypass at bulky benzo[a]pyrene-derived lesions.

引用

页码：209 / 219

页数：11

共 81 条

[11] Molecular modeling benzo[a]pyrene N2-dG adducts in the two overlapping active sites of the Y-family DNA polymerase Dpo4 [J].