DNA Polymerase λ Protects Mouse Fibroblasts against Oxidative DNA Damage and Is Recruited to Sites of DNA Damage/Repair

DNA polymerase λ (pol λ) 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...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-09, Vol.280 (36), p.31641-31647
Main Authors: Braithwaite, Elena K., Kedar, Padmini S., Lan, Li, Polosina, Yaroslava Y., Asagoshi, Kenjiro, Poltoratsky, Vladimir P., Horton, Julie K., Miller, Holly, Teebor, George W., Yasui, Akira, Wilson, Samuel H.
Format: Article
Language:English
Subjects:
Animals
Cell Line
DNA Damage - genetics
DNA Damage - physiology
DNA Glycosylases - metabolism
DNA Polymerase beta - deficiency
DNA Polymerase beta - genetics
DNA Polymerase beta - physiology
DNA Repair - genetics
DNA Repair - physiology
Fibroblasts - physiology
HeLa Cells
Humans
Mice
Oxidants - chemistry
Oxidation-Reduction
Pentoxyl - analogs & derivatives
Pentoxyl - pharmacology
Uracil-DNA Glycosidase
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Summary:DNA polymerase λ (pol λ) 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 λ null mouse fibroblasts are hypersensitive to oxidative DNA damaging agents, suggesting a role of pol λ in protection of cells against the cytotoxic effects of oxidized DNA. Additionally, pol λ 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 λ protects cells against oxidative stress and suggest that it participates in oxidative DNA damage base excision repair.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C500256200