Demethylаtiоn оf DNA nucleоtides is а cruciаl biological process that ensures the proper regulation of gene expression and maintains DNA integrity. DNA methylation typically involves the addition of a methyl group to the 5th carbon of cytosine residues in CpG dinucleotides, a modification that plays an essential role in controlling gene activity, silencing transposons, and maintaining genomic stability. While methylation is necessary for normal cellular function, excessive or inappropriate methylation patterns can lead to silencing of key regulatory genes, especially tumor suppressor genes, contributing to the development of diseases such as cancer. Therefore, the process of demethylation, which removes methyl groups from DNA, is equally vital for resetting epigenetic marks and protecting against aberrant methylation patterns. Demethylation can occur actively or passively. Passive demethylation happens during DNA replication when the newly synthesized strand is not methylated, leading to a gradual loss of methylation over successive cell divisions. In contrast, active demethylation involves direct enzymatic removal of methyl groups from DNA. This process is facilitated by enzymes such as the Ten-Eleven Translocation (TET) family, which oxidizes 5-methylcytosine (5mC) to produce 5-hydroxymethylcytosine (5hmC), followed by further oxidative steps leading to the eventual replacement of the modified base with an unmethylated cytosine via base excision repair (BER). This active demethylation pathway is critical for dynamic regulation of gene expression, particularly during development, cellular reprogramming, and in response to environmental changes. The demethylation of DNA nucleotides is essential for maintaining DNA integrity. DNA methylation patterns are tightly regulated, and any disruption in this balance can lead to mutations or genomic instability. For example, the repair of O6-methylguanine, a cytotoxic and mutagenic lesion caused by alkylating agents, relies on specific enzymes like O6-methylguanine-DNA methyltransferase (MGMT). MGMT removes the aberrant methyl group from the O6 position of guanine, directly reversing the damage and preventing the mispairing of O6-methylguanine with thymine, which could lead to Gto Atransitions during replication. By correcting such damage, demethylation processes help preserve the accuracy of the DNA sequence and prevent mutations that could promote carcinogenesis or other genetic disorders. What is the main amino acid residue esponsible for the activity of methyltransferase?