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Originally published In Press as doi:10.1074/jbc.C500256200 on July 7, 2005

J. Biol. Chem., Vol. 280, Issue 36, 31641-31647, September 9, 2005
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DNA Polymerase {lambda} Protects Mouse Fibroblasts against Oxidative DNA Damage and Is Recruited to Sites of DNA Damage/Repair*

Elena K. Braithwaite{ddagger}, Padmini S. Kedar{ddagger}, Li Lan§, Yaroslava Y. Polosina¶, Kenjiro Asagoshi{ddagger}, Vladimir P. Poltoratsky{ddagger}, Julie K. Horton{ddagger}, Holly Miller¶, George W. Teebor||, Akira Yasui§, and Samuel H. Wilson{ddagger}**

From the {ddagger}Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, the §Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, 980-8575 Sendai, Japan, the Laboratory of Chemical Biology, Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794-8651, and the ||Department of Pathology, New York University School of Medicine, New York, New York 10016

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.


Received for publication, June 15, 2005 , and in revised form, July 5, 2005.

* This work was supported in part by the Intramural Research Program of the National Institutes of Health, NIEHS. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** To whom correspondence should be addressed. Tel.: 919-541-3267; Fax: 919-541-3592; E-mail: wilson5{at}niehs.nih.gov.


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