Demethylation_of_5-methylcytosine.svg


Summary

Description
English: Demethylation of 5-Methylcytosine (5mC) in DNA. As reviewed in 2018, [1] 5mC is oxidized by the ten-eleven translocation (TET) family of dioxygenases ( TET1 , TET2 , TET3 ) to generate 5-hydroxymethylcytosine (5hmC). In successive steps TET enzymes further hydroxylate 5hmC to generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Thymine-DNA glycosylase (TDG) recognizes the intermediate bases 5fC and 5caC and excises the glycosidic bond resulting in an apyrimidinic site ( AP site ). In an alternative oxidative deamination pathway, 5hmC can be oxidatively deaminated by activity-induced cytidine deaminase/apolipoprotein B mRNA editing complex (AID/APOBEC) deaminases to form 5-hydroxymethyluracil (5hmU) or 5mC can be converted to thymine (Thy). 5hmU can be cleaved by TDG, single-strand-selective monofunctional uracil-DNA glycosylase 1 ( SMUG1 ), Nei-Like DNA Glycosylase 1 ( NEIL1 ), or methyl-CpG binding protein 4 ( MBD4 ). AP sites and T:G mismatches are then repaired by base excision repair (BER) enzymes to yield cytosine (Cyt).
Date
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Author Bernstein0275 , User:Innerstream

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  1. (2018). " The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders ". Front Mol Neurosci 11 : 169. DOI : 10.3389/fnmol.2018.00169 . PMID 29875631 . PMC : 5975432 .

Captions

Demethylation pathways for 5-Methylcytosine

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3 September 2018

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