There are many ways that gene expression is controlled in eukaryotes, but methylation of DNA (not to be confused with histone methylation) is a common epigenetic signaling tool that cells use to lock genes in the \"off\" position. Methylation is an important component in numerous cellular processes, including embryonic development, genomic imprinting, X-chromosome inactivation, and preservation of chromosome stability.DNA methylation occurs at the cytosine bases of eukaryotic DNA, which are converted to 5-methylcytosine by DNA-methyltransferase (DNMT; EC 2.1.1.37) enzymes using S-adenosyl methionine (SAM) as the methyl donor. The altered cytosine residues are usually immediately adjacent to a guanine nucleotide, resulting in two methylated cytosine residues sitting diagonally to each other on opposing DNA strands. Different members of the DNMT family of enzymes act either as de novo DNMTs, putting the initial pattern of methyl groups in place on a DNA sequence, or as maintenance DNMTs, copying the methylation from an existing DNA strand to its new partner after replication. Although patterns of DNA methylation appear to be relatively stable in somatic cells, patterns of histone methylation can change rapidly during the course of the cell cycle. Despite this difference, several studies have indicated that DNA methylation and histone methylation at certain positions are connected.O6-methylguanine lesions, which are widely accepted as the primary cytotoxic lesions induced by methylating agents, are efficiently repaired by the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT; EC 2.1.1.63) that removes the methyl adducts from the O6 positions of guanine by transferring it to its internal cysteine residues, resulting in its own inactivation (mechanism of action is the opposite of most DNA methyltransferases that transfer a methyl group to DNA). It is ubiquitously expressed, highly conserved, and vital to the maintenance of DNA integrity. Evidendce has been accumulated that tumors expressing MGMT are remarkably resistant to methylating agents, and this problem might be circumvented by specific inhibitors of MGMT.