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

Elena K. Braithwaite, Padmini S. Kedar, Li Lan, Yaroslava Y. Polosina, Kenjiro Asagoshi, Vladimir P. Poltoratsky, Julie K. Horton, Holly Miller, George W. Teebor, Akira Yasui, Samuel H. Wilson

    Research output: Contribution to journalArticlepeer-review

    97 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)31641-31647
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume280
    Issue number36
    DOIs
    Publication statusPublished - 2005 Sep 9

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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