[The mechanism of replicative and post-replicative DNA methylation as a generator of mutations in a cell].
The functional role of enzymatic DNA methylation in eukaryotes is still obscure even 45 years after its discovery. In the present paper the analysis of various aspects of DNA methylation has been made from the point of view of a common functional model considering the system as a generator of 5mC-->T mutations in the cell. The mechanism and consequences of the reactions have been described in detail, from the 5mC residue deamination during replicative DNA methylation and repair of G.T-mispairs to production of hemimethylated sites in DNA and their postreplicative methylation. It was shown that the loss of the most part of the 5mC residues from DNA during the lifespan proceeds with aging both of organism's tissues and of cell cultures. Evidence was obtained that this is the result of gradual accumulation of 5mC-->T + C transitions in the genome during each cell division. Such substitutions take place 10 times more often in methylated sites *CG than in any other sites of DNA. They disproportionally contribute to general mutagenesis and may be a cause of many hereditary human diseases. The conclusion has been made that DNA methylation can be considered as a genetically programmed mechanism for accumulating mutations with aging.
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D044503:5-Methylcytosine; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication; D016678:Genome; D006801:Humans; D008745:Methylation; D009154:Mutation; D013941:Thymine / Q000378:metabolism
D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA; D013941:Thymine
O mekhanizme replikativnogo i postreplikativnogo metilirovaniia DNK kakgeneratore mutatsiĭ v kletke.