title: Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia.
abstract: 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.
authors: Department of Microbiology and Pediatric Research, Centre for Molecular Biology and Neurosciences, University of Oslo and Oslo University Hospital, Rikshospitalet, Nydalen, N-0424 Oslo, Norway.
authors: Yngve
authors: Y
authors: Sejersted
authors: Gunn A
authors: GA
authors: Hildrestrand
authors: David
authors: D
authors: Kunke
authors: Veslemøy
authors: V
authors: Rolseth
authors: Silje Z
authors: SZ
authors: Krokeide
authors: Christine G
authors: CG
authors: Neurauter
authors: Rajikala
authors: R
authors: Suganthan
authors: Monica
authors: M
authors: Atneosen-Åsegg
authors: Aaron M
authors: AM
authors: Fleming
authors: Ola D
authors: OD
authors: Saugstad
authors: Cynthia J
authors: CJ
authors: Burrows
authors: Luisa
authors: L
authors: Luna
authors: Magnar
authors: M
authors: Bjørås
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004249:DNA Damage; D004277:DNA, Single-Stranded; D004706:Endodeoxyribonucleases / Q000235:genetics* / Q000378:metabolism; D006827:Hydantoins / Q000378:metabolism; D000860:Hypoxia / Q000235:genetics*; D007511:Ischemia / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis; D013234:Stem Cells / Q000166:cytology
chemical_list: D004277:DNA, Single-Stranded; D006827:Hydantoins; D004706:Endodeoxyribonucleases; C540052:NEIL3 protein, mouse