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Human OGG1 polymorphisms resulting in reduced DNA repair associate with an increased risk for disorders like cancer and diabetes, but the role of OGG1 in brain development is unclear. Herein, we show that Ogg1 knockout mice at 2\u20133\u2009months of age exhibit enhanced gene- and sex-dependent DNA damage (strand breaks) and decreased epigenetic DNA methylation marks (5-methylcytosine, 5-hydroxymethylcytosine), both of which were associated with increased cerebellar calbindin levels, reduced hippocampal postsynaptic function, altered body weight with age and disorders of brain function reflected in behavioral tests for goal-directed repetitive behavior, anxiety and fear, object recognition and spatial memory, motor coordination and startle response. These results suggest that OGG1 plays an important role in normal brain development, possibly via both its DNA repair activity and its role as an epigenetic modifier, with OGG1 deficiencies potentially contributing to neurodevelopmental disorders.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac003","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T20:14:18Z","timestamp":1641932058000},"page":"93-111","source":"Crossref","is-referenced-by-count":15,"title":["DNA Damage and Repair and Epigenetic Modification in the Role of Oxoguanine Glycosylase 1 in Brain Development"],"prefix":"10.1093","volume":"187","author":[{"given":"Shama","family":"Bhatia","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada"},{"name":"Centre for Pharmaceutical Oncology, Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliyas","family":"Arslan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis David","family":"Rodriguez-Hernandez","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Bonin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2241-9107","authenticated-orcid":false,"given":"Peter G","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada"},{"name":"Centre for Pharmaceutical Oncology, Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada"},{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"2022050912324653500_kfac003-B1","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1093\/cercor\/bhj114","article-title":"Ventromedial prefrontal cortex is obligatory for consolidation and reconsolidation of object recognition memory","volume":"16","author":"Akirav","year":"2006","journal-title":"Cereb. 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