title: DNA demethylation pathways: Additional players and regulators.
abstract: DNA demethylation can occur passively by "dilution" of methylation marks by DNA replication, or actively and independently of DNA replication. Direct conversion of 5-methylcytosine (5mC) to cytosine (C), as originally proposed, does not occur. Instead, active DNA methylation involves oxidation of the methylated base by ten-eleven translocations (TETs), or deamination of the methylated or a nearby base by activation induced deaminase (AID). The modified nucleotide, possibly together with surrounding nucleotides, is then replaced by the BER pathway. Recent data clarify the roles and the regulation of well-known enzymes in this process. They identify base excision repair (BER) glycosylases that may cooperate with or replace thymine DNA glycosylase (TDG) in the base excision step, and suggest possible involvement of DNA damage repair pathways other than BER in active DNA demethylation. Here, we review these new developments.
authors.affiliation: International Institute of Molecular and Cell Biology, Warsaw, Poland.|Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bochtler
authors.affiliation: International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kolano
authors.affiliation: Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xu
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism*; D000818:Animals; D003564:Cytidine Deaminase / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation; D004260:DNA Repair; D044127:Epigenesis, Genetic; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism
chemical_list: D044503:5-Methylcytosine; D004247:DNA; D006899:Mixed Function Oxygenases; D003564:Cytidine Deaminase
keywords: 5-carboxylcytosine; 5-formylcytosine; 5-hydroxymethylcytosine; 5-hydroxymethyluracil; AID; TDG; TET; active DNA demethylation; deamination; oxidation