Active DNA demethylation pathways in plants and animals. Arabidopsis bifunctional DNA glycosylases, such as ROS1 and DME, can directly excise 5-mC and then cleave the DNA backbone at the abasic site, resulting in a gap that is filled with an unmodified cytosine through the BER pathway. In mammals where no ROS1 ortholog has been identified to date, 5-mC can undergo deamination and/or hydroxylation before being excised by DNA mismatch repair glycosylases, which triggers the BER pathway to complete the active demethylation process. See text for details.