Deamination of 5-Methylcytosine Residues in Mammalian Cells

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Abstract


DNA demethylation in mammalia occurs after fertilization and during embryogenesis and accompanies cell aging and cancer transformation. With the help of the primer extension reaction, MALDI MS and DNA cleavage by thymine DNA glycosylase deamination of 5-methylcytosine residues has been shown to take place when the model methylated DNA duplexes are treated with nuclear extracts from the cell lines СНO, HeLa, and Skov3. The hypothesis that deamination of 5-methylcytosine is the first stage of demethylation in mammalia has been postulated.

Active DNA demethylation in mammalia is necessary for the proper development of the organism, formation of the immune response, and memory. DNA demethylation accompanies the emergence of various diseases and aging. Global demethylation is observed in the paternal pronuclei in the embryos of mice [1], rats, pigs, cows, and humans [2], as well as in their germ cells. It provides epigenetic reprogramming and specific gene expression. Methylation and demethylation of DNA in the cells of the nervous system has an influence on synaptic plasticity and memory formation. DNA methylation is necessary for the inactivation of the gene pp1 that suppresses memory processes; whereas active DNA demethylation is associated with activation of the gene reelin that promotes the formation of memory in rats [3]. Also, active DNA demethylation is necessary for normal neurogenesis in the embryos of fish Danio rerio. Suppression of the expression of protein Gadd45a (DNA-damage-inducible protein 45 alpha) or other proteins involved in the process of demethylation leads to the death of neurons as a result of hypermethylation and suppression of the genes responsible for neurogenesis [4].

E V Gromenko

Department of Chemistry, Lomonosov Moscow State University

P V Spirin

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

E A Kubareva

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

E A Romanova

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

V S Prassolov

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

O V Shpanchenko

Department of Chemistry, Lomonosov Moscow State University

O A Dontsova

Department of Chemistry, Lomonosov Moscow State University; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

Email: olgash@genebee.msu.ru

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Copyright (c) 2009 Gromenko E.V., Spirin P.V., Kubareva E.A., Romanova E.A., Prassolov V.S., Shpanchenko O.V., Dontsova O.A.

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