Hypersensitivity of mouse NEIL1-knockdown cells to hydrogen peroxide during S phase

Oxidative base damage occurs spontaneously due to reactive oxygen species generated as byproducts of respiration and other pathological processes in mammalian cells. many oxidized bases are mutagenic and/or toxic,and most are repaired through the base excision repair pathway. human endonuclease viii-like protein 1 (hneil1) is thought to play an important role during the s phase of the cell cycle by removing oxidized bases in dna replication fork-like (bubble) structures,and the protein level of hneil1 is increased in s phase. compared with hneil1,there is relatively little information on the properties of the mouse ortholog mneil1. since mouse cell nuclei lack endonuclease iii-like protein (nth) activity,in contrast to human cell nuclei,mneil1 is a major dna glycosylase for repair of oxidized pyrimidines in mouse nuclei. in this study,we made mneil1-knockdown cells using an shrna expression vector and examined the cell cycle-related variation in hydrogen peroxide (h2o2) sensitivity. hypersensitivity to h2o2 caused by mneil1 knockdown was more significant in s phase than in g1 phase,suggesting that mneil1 has an important role during s phase,similarly to hneil1. © 2014 the author.