Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia

Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18802-7. doi: 10.1073/pnas.1106880108. Epub 2011 Nov 7.


Neural stem/progenitor cell proliferation and differentiation are required to replace damaged neurons and regain brain function after hypoxic-ischemic events. DNA base lesions accumulating during hypoxic-ischemic stress are removed by DNA glycosylases in the base-excision repair pathway to prevent cytotoxicity and mutagenesis. Expression of the DNA glycosylase endonuclease VIII-like 3 (Neil3) is confined to regenerative subregions in the embryonic and perinatal brains. Here we show profound neuropathology in Neil3-knockout mice characterized by a reduced number of microglia and loss of proliferating neuronal progenitors in the striatum after hypoxia-ischemia. In vitro expansion of Neil3-deficient neural stem/progenitor cells revealed an inability to augment neurogenesis and a reduced capacity to repair for oxidative base lesions in single-stranded DNA. We propose that Neil3 exercises a highly specialized function through accurate molecular repair of DNA in rapidly proliferating cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • DNA Damage
  • DNA, Single-Stranded
  • Endodeoxyribonucleases / genetics*
  • Endodeoxyribonucleases / metabolism
  • Hydantoins / metabolism
  • Hypoxia / genetics*
  • Ischemia / genetics*
  • Mice
  • Mice, Knockout
  • Mitosis
  • Neural Stem Cells / cytology
  • Neurogenesis
  • Stem Cells / cytology


  • DNA, Single-Stranded
  • Hydantoins
  • Endodeoxyribonucleases
  • NEIL3 protein, mouse