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DNA cytosine methyltransferases catalyze two different reactions: transfer methyl groups for covalent modification of cytosine residues and deamination of a portion of newly formed 5mC with the emergence of 5mC-to-T substitutions in genome (see animation). This is the first step in a cascade of molecular events leading to hotspots for various types of mutations at sites of methylation. These mutations occur with each DNA replication and continually accumulate over lifespan, causing inactivation of genes and disintegration of the genome machinery. Thus, DNA methylation is a powerful endogenous generator of mutations that may be a mechanism for cell aging and death or immortalization.

 

 

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