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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.

SUBMITTER: Sejersted Y 

PROVIDER: S-EPMC3219145 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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

Sejersted Yngve Y   Hildrestrand Gunn A GA   Kunke David D   Rolseth Veslemøy V   Krokeide Silje Z SZ   Neurauter Christine G CG   Suganthan Rajikala R   Atneosen-Åsegg Monica M   Fleming Aaron M AM   Saugstad Ola D OD   Burrows Cynthia J CJ   Luna Luisa L   Bjørås Magnar M  

Proceedings of the National Academy of Sciences of the United States of America 20111107 46


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 neur  ...[more]

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