Computational Insights in DNA Methylation: Catalytic and Mechanistic
Elucidations for Forming 3-Methyl Cytosine
Abstract
abundantly occurring methylation process at CpG island, which has been
well-known as an epigenetic modification linked to many human’s
diseases. Recently, another methylation approach has been discovered to
show that DNA methyltransferases (DNMTs) promote the addition of methyl
group at position 3 to yield 3mC. The existence of 3mC can cause severe
damages to the DNA strand, such as blocking its replication, repair, and
transcription, affecting its stability, and initiating a double-strand
DNA break. To gain a deeper insight into the formation of 3mC, we have
performed density functional theory (DFT) modeling studies at different
levels of theory to clearly map out the mechanistic details for this new
methylation approach. Our computed results are in harmony with pertinent
experimental observations and shed light on a crucial off-target
activity of DNMTs.