Demethylation_of_5-methylcytosine.svg
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Summary
Description Demethylation of 5-methylcytosine.svg |
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 | |
Source | Own work |
Author | Bernstein0275 , User:Innerstream |
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- ↑ (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 .