DNA polymerase lambda protects mouse fibroblasts against oxidative DNA damage and is recruited to sites of DNA damage/repair.
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.
Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Elena K
EK
Braithwaite
Padmini S
PS
Kedar
Li
L
Lan
Yaroslava Y
YY
Polosina
Kenjiro
K
Asagoshi
Vladimir P
VP
Poltoratsky
Julie K
JK
Horton
Holly
H
Miller
George W
GW
Teebor
Akira
A
Yasui
Samuel H
SH
Wilson
D000818:Animals; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D045647:DNA Glycosylases / Q000378:metabolism; D019951:DNA Polymerase beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010432:Pentoxyl / Q000031:analogs & derivatives / Q000494:pharmacology; D051981:Uracil-DNA Glycosidase
D016877:Oxidants; C008055:5-hydroxymethyluracil; D010432:Pentoxyl; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta; D045647:DNA Glycosylases; C498095:SMUG1 protein, human; D051981:Uracil-DNA Glycosidase