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 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.