The lyase activity of the DNA repair protein β-polymerase protects from DNA-damage-induced cytotoxicity

被引：289

作者：

Sobol, RW ^{[1
]}

Prasad, R ^{[1
]}

Evenski, A ^{[1
]}

Baker, A ^{[1
]}

Yang, XP ^{[1
]}

Horton, JK ^{[1
]}

Wilson, SH ^{[1
]}

机构：

[1] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA

来源：

NATURE | 2000年 / 405卷 / 6788期

关键词：

D O I：

10.1038/35015598

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Small DNA lesions such as oxidized or alkylated bases are repaired by the base excision repair (BER) pathway(1). BER includes removal of the damaged base by a lesion-specific DNA glycosylase, strand scission by apurinic/apyrimidinic endonuclease, DNA resynthesis and ligation(2). BER may be further subdivided into DNA beta-polymerase (beta-pol)-dependent single-nucleotide repair and beta-pol-dependent or -independent long patch repair subpathways(3-6). Two important enzymatic steps in mammalian single-nucleotide BER are contributed by beta-pol: DNA resynthesis of the repair patch and lyase removal of 5'-deoxyribose phosphate (dRP)(2). Fibroblasts from beta-pol null mice are hypersensitive to monofunctional DNA-methylating agents, resulting in increases in chromosomal damage, apoptosis and necrotic cell death(3,7). Here we show that only the dRP lyase activity of beta-pol is required to reverse methylating agent hypersensitivity in beta-pol null cells. These results indicate that removal of the dRP group is a pivotal step in BER in vivo. Persistence of the dRP moiety in DNA results in the hypersensitivity phenotype of beta-pol null cells and may signal downstream events such as apoptosis and necrotic cell death.

引用

页码：807 / 810

页数：5

共 27 条

[1] DNA polymerase beta: Structure-fidelity relationship from pre-steady-state kinetic analyses of all possible correct and incorrect base pairs for wild type and R283A mutant [J].