Neil DNA glycosylases promote substrate turnover by Tdg during DNA demethylation.
Nat Struct Mol Biol
; 23(2): 116-124, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26751644
ABSTRACT
DNA 5-methylcytosine is a dynamic epigenetic mark with important roles in development and disease. In the Tet-Tdg demethylation pathway, methylated cytosine is iteratively oxidized by Tet dioxygenases, and unmodified cytosine is restored via thymine DNA glycosylase (Tdg). Here we show that human NEIL1 and NEIL2 DNA glycosylases coordinate abasic-site processing during TET-TDG DNA demethylation. NEIL1 and NEIL2 cooperate with TDG during base excision TDG occupies the abasic site and is displaced by NEILs, which further process the baseless sugar, thereby stimulating TDG-substrate turnover. In early Xenopus embryos, Neil2 cooperates with Tdg in removing oxidized methylcytosines and specifying neural-crest development together with Tet3. Thus, Neils function as AP lyases in the coordinated AP-site handover during oxidative DNA demethylation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metilação de DNA
/
DNA Glicosilases
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Timina DNA Glicosilase
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DNA Liase (Sítios Apurínicos ou Apirimidínicos)
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Reparo do DNA
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Struct Mol Biol
Ano de publicação:
2016
Tipo de documento:
Article