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

Abstract
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.
AuthorsRyohei Yamamoto, Yukari Ohshiro, Tatsuhiko Shimotani, Mizuki Yamamoto, Satoshi Matsuyama, Hiroshi Ide, Kihei Kubo
JournalJournal of radiation research (J Radiat Res) Vol. 55 Issue 4 Pg. 707-12 (Jul 2014) ISSN: 1349-9157 [Electronic] England
PMID24706997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.
Chemical References
  • RNA, Small Interfering
  • Hydrogen Peroxide
  • DNA Glycosylases
  • NEIL1 protein, human
  • Neil1 protein, mouse
Topics
  • Animals
  • Cells, Cultured
  • DNA Damage
  • DNA Glycosylases (antagonists & inhibitors, genetics, metabolism)
  • DNA Repair (drug effects)
  • G1 Phase (drug effects)
  • Gene Knockdown Techniques
  • Humans
  • Hydrogen Peroxide (pharmacology)
  • L Cells
  • Mice
  • RNA, Small Interfering (genetics)
  • S Phase (drug effects)

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