DNA polymerase λ protects mouse fibroblasts against oxidative DNA damage and is recruited to sites of DNA damage/repair

被引：95

作者：

Braithwaite, EK

Kedar, PS

Lan, L

Polosina, YY

Asagoshi, K

Poltoratsky, VP

Horton, JK

Miller, H

Teebor, GW

Yasui, A

Wilson, SH

机构：

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

[2] Tohoku Univ, Inst Dev Aging & Canc, Dept Mol Genet, Sendai, Miyagi 9808575, Japan

[3] SUNY Stony Brook, Dept Pharmacol Sci, Biol Chem Lab, Stony Brook, NY 11794 USA

[4] NYU, Dept Pathol, New York, NY 10016 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2005年 / 280卷 / 36期

关键词：

D O I：

10.1074/jbc.C500256200

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 polymerase lambda ( pol lambda) is a member of the X family of DNA polymerases that has been implicated in both base excision repair and non-homologous end joining through in vitro studies. However, to date, no phenotype has been associated with cells deficient in this DNA polymerase. Here we show that pol lambda null mouse fibroblasts are hypersensitive to oxidative DNA damaging agents, suggesting a role of pol lambda in protection of cells against the cytotoxic effects of oxidized DNA. Additionally, pol lambda co-immunoprecipitates with an oxidized base DNA glycosylase, single-strand-selective monofunctional uracil-DNA glycosylase (SMUG1), and localizes to oxidative DNA lesions in situ. From these data, we conclude that pol lambda protects cells against oxidative stress and suggest that it participates in oxidative DNA damage base excision repair.

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页码：31641 / 31647

页数：7

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