3-methylcytosine in cancer: an underappreciated methyl lesion?

DNA methylation is an important epigenetic mark modulating many developmental and potentially pathological processes. Changes in DNA methylation are often observed in cancer and, cytosine methylation in particular, can be mediated enzymatically, resulting in, for example, 5-methylcytosine (5mC) or chemically, resulting in, for example, 3-methylcytosine (3mC) [1,2]. If base pairing is affected by methylation as it is by 3mC, it can lead to methyl lesions which, if refractory to repair, can add to the mutational burden of affected cells. Here, we explore some underappreciated properties of 3mC in cancer.

Arising from nonenzymatic methylation by endogenous or exogenous methyl donors, chemically mediated methyl lesions can have disruptive effects on local DNA functionality [3]. In nonmalignant cells, it can be expected that DNA repair pathways are intact and that any lesions will be repaired or, if the damage confers no selective growth advantage and is potentially lethal to the cell, programmed cell death (apoptotic) pathways will be activated. Conversely, in cancer where DNA repair mechanisms and apoptotic pathways are compromised due to somatic mutations, these methyl lesions and their effects on DNA are likely to persist.

Click here to view the full article in Epigenomics.