Regulation of the DNA methylation machinery and its role in cellular transformation

Deoxyribonucleic acid (DNA) methylation, a covalent modification of the genome, is emerging as an important player in the regulation of gene expression. This chapter discusses the different components of the DNA methylation machinery responsible for replicating the DNA methylation pattern. A number of DNA methyltransferases (DNMT) have been identified and a demethylase has recently been reported. Because the DNA methylation pattern is critical for gene expression programs, the cell possesses a number of mechanisms to coordinate DNA replication and methylation. DNMT levels are regulated, with the cell cycle, and are induced upon the entry into the S-phase of the cell cycle. Overexpression of DNMT1 is probably not responsible for the aberrant methylation of tumor suppressor genes. Unraveling how the different components of the DNA methylation machinery interact to replicate the DNA methylation pattern and how they are disrupted in cancer, it is critical to understand the molecular mechanisms of cancer.