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Nat Struct Mol Biol 2016 Feb 01;232:116-124. doi: 10.1038/nsmb.3151.
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Neil DNA glycosylases promote substrate turnover by Tdg during DNA demethylation.

Schomacher L , Han D , Musheev MU , Arab K , Kienhöfer S , von Seggern A , Niehrs C .

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.

PubMed ID: 26751644
PMC ID: PMC4894546
Article link: Nat Struct Mol Biol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: apex1 egr2 en2 hprt1 mbd4 mpg neil1 neil2 neil3 nog nthl1 ogg1 smug1 snai2 sox10 tcf21 tdg tet3 twist1 wnt8a
Morpholinos: neil1 MO1 neil2 MO1 neil2 MO2 tdg MO1 tet3 MO1 tet3 MO3

Article Images: [+] show captions
References [+] :
Arab, Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. 2014, Pubmed