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- W2255354927 abstract "During oxidative DNA demethylation, Neil DNA glycosylases stimulate processing of abasic sites generated by Tdg, which excises 5-methylcytosine oxidation products generated by Tet dioxygenases, promoting restoration of unmodified cytosines via base excision repair. 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." @default.
- W2255354927 created "2016-06-24" @default.
- W2255354927 creator A5015718558 @default.
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- W2255354927 date "2016-01-11" @default.
- W2255354927 modified "2023-10-18" @default.
- W2255354927 title "Neil DNA glycosylases promote substrate turnover by Tdg during DNA demethylation" @default.
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- W2255354927 doi "https://doi.org/10.1038/nsmb.3151" @default.
- W2255354927 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4894546" @default.
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- W2255354927 hasPublicationYear "2016" @default.
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