Figure 1. Potential roles of DNA methylation in genome maintenance.

A simplified model depicting the putative roles of DNA methylation in the maintenance of genome integrity. DNA is methylated commonly at CpG sites, transposable elements, sites of tissue-specific gene silencing, X-chromosome inactivation and genome imprinting. DNA can undergo spontaneous deamination causing mutations or encounter roadblocks during replication from secondary structures such as R-loops and G-quadruplexes (G4), which may confer aberrant methylation patterns across the genome affecting gene transcription or impacting DNA DSB repair in response to DNA damage. Collectively, DNA methylation has the potential to affect the DDR as illustrated. Likewise,alterations in these pathways could also alter DNA methylation, which warrants consideration.