The capacity to remove 8-oxoG is enhanced in newborn neural stem/progenitor cells and decreases in juvenile mice and upon cell differentiation.
In mammalian cells, 8-oxoguanine DNA glycosylase-1 (OGG1) is the main DNA glycosylase for the removal of 8-oxoguanine (8-oxoG). 8-oxoG, one of the most common products of the oxidative attack of DNA, is a premutagenic lesion that accumulates spontaneously at high frequencies in the genome. In this study, Ogg1 mRNA expression was detected throughout embryonic development in mice. In situ hybridization showed that in the neonatal brain, Ogg1 expression was detected in a distinct layer of cells in the medial wall of the lateral ventricle, which may correspond to ependymal cells, and in some scattered cells in the subventricular zone (SVZ), a brain region rich in neural stem/progenitor cells. Using neurospheres as a model for the study of neural stem/progenitor cells, we found that both the expression and activity of Ogg1 were high in neurospheres derived from newborn mice and decreased in adults and upon induction of cell differentiation. Furthermore, Ogg1 was shown to be the major DNA glycosylase initiating 8-oxoG repair in neurospheres. Our results strongly indicate that enhanced DNA repair capacity is an important mechanism by which neural stem/progenitor cells maintain their genome.
Hildrestrand
Gunn A
GA
Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, Rikshospitalet-Radiumhospitalet HF, 0027 Oslo, Norway.
Diep
Dzung B
DB
Kunke
David
D
Bolstad
Nils
N
Bjørås
Magnar
M
Krauss
Stefan
S
Luna
Luisa
L
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D045647:DNA Glycosylases / Q000235:genetics* / Q000502:physiology*; D004260:DNA Repair; D005347:Fibroblasts / Q000166:cytology; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
D012333:RNA, Messenger; D006151:Guanosine; C046215:8-hydroxyguanosine; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse