The mechanisms through which environmental and dietary factors modulate repair are still unclear but may include dysregulation of gene altered epigenetic markings. In a mouse model, we investigated the maternal folate depletion during pregnancy and lactation, and high-fat from weaning, on base excision repair (BER) and DNA methylation and selected BER-related genes in the brain of adult offspring. While folate depletion did not affect BER activity of the mothers, BER increased in offspring at weaning (P=0.052). In the long term, as observed in 6-mo- offspring, the double insult, i.e., maternal low-folate supply and high- feeding from weaning, decreased BER activity significantly in the cerebellum, hippocampus, and subcortical regions (P</=0.017). This fall activity was associated with small changes in methylation or expression BER-related genes. Maternal folate depletion led to slightly increased DNA damage levels in subcortical regions of adult offspring, which may sensitivity to oxidative stress and predispose to neurological summary, our data suggest that low-folate supply during early life may epigenetic mark that can predispose the offspring to further dietary causing adverse effects during adult life.-Langie, S. A. S., Gorniak, J. P., Halley-Hogg, K. J. A., Oxley, D., van Schooten, F. J., R. W. L., McKay, J. A., Mathers, J. C. Maternal folate depletion and feeding from weaning affects DNA methylation and DNA repair in brain of offspring.