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In this invited review for Trends in Genetics, Marketa Tomkova and Benjamin Schuster-Böckler explore how epigenetic modification of DNA influences mutagenesis. Some modifications such as methylation of DNA on cytosine bases are well known to increase the rate of mutation through a spontaneous chemical change to thymine. DNA modifications also affect the likelihood of DNA mutagenesis by both external factors e.g. UV light or smoking and cell-intrinsic processes e.g. DNA replication. This review discusses what is known to date and some of the outstanding questions in the field.