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Epigenetic DNA modifications are essential for normal cell function in vertebrates, but they can also be hotspots of mutagenesis. Methylcytosine in particular has long been known to be less stable than other nucleotides and spontaneously deaminates to thymine. Beyond this well-established phenomenon, however, the influence of epigenetic marks on mutagenesis has recently become an active field of investigation. In this review, we summarize current knowledge of the interactions between different DNA modifications and other mutagenic processes. External mutagens, such as UV light or smoking carcinogens, affect modified cytosines differently from unmodified ones, and modified cytosine can in some cases be protective rather than mutagenic. Notably, cell-intrinsic processes, such as DNA replication, also appear to influence the mutagenesis of modified cytosines. Altogether, evidence is accumulating to show that epigenetic changes have a profound influence on tissue-specific mutation accumulation.

Original publication

DOI

10.1016/j.tig.2018.04.005

Type

Journal article

Journal

Trends Genet

Publication Date

08/2018

Volume

34

Pages

627 - 638

Keywords

5-hydroxymethylcytosine, 5-methylcytosine, CpG dinucleotides, DNA modifications, mutagenesis, Animals, CpG Islands, DNA, DNA Methylation, DNA Repair, DNA Replication, Epigenesis, Genetic, Humans, Mutagenesis, Mutation, Smoking, Sunlight, Ultraviolet Rays