Role of DNA Methylation in Genome Stability

Genome instability is detrimental to cell survival. It is manifested by high mutation frequencies driven by changes in nucleic acid sequences, chromosome rearrangement, or aneuploidy. In close association with these genetic events is the malfunction in DNA damage-repair pathways, as they generally correct mutations or prevent them from taking place through a series of supervising and correcting mechanisms. Epigenetic modifications, especially DNA methylation, contribute to maintaining genetic content in multiple ways. Base mismatch errors arising from replication and homologous recombination are recognized and repaired mainly through the DNA mismatch repair (MMR) system. DNA methylation and DNA methyltransferases assist in recognizing mismatches while also contributing to genome stability by regulating MMR gene transcription. Intensive DNA methylation at heterochromatin repeats stabilizes such domains from translocation and undesired spreading, ensuring the appropriate functions of centromeres and telomeres, as well as genetic integrity. This chapter aims to review the major influences of DNA methylation on sustaining genetic stability.