Fig. 6

Oxidative lesions in sperm impair active DNA demethylation at the paternal genome in zygotes. The model shows the link of BER to DNA damage and active DNA demethylation. On the left, it is shown how a putative DNA glycosylase recognizes 5mC or its modified forms, giving rise to abasic sites that via the subsequent enzymes of the BER pathway (i.e. APE1 and XRCC1) allows the incorporation of unmodified cytosines. On the right, it is shown how oxidative lesions in sperm can impair DNA demethylation. Two models are here shown. In the first case, the presence of abasic sites that are established by OGG1 prior fertilization in sperm sequester XRCC1 at the expense of DNA demethylation activities, where recognition and excision of 5mC or its derivative is initiated only post-fertilization. The second model suggests that DNA lesions inhibit the activity of the DNA glycosylase(s) responsible for the DNA demethylation. In both cases, the final product is a DNA that is repaired but still contains methylated cytosines