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The DNA methylation cycle encompasses the reversible addition and removal of methyl groups to cytosine (and sometimes adenine) bases in DNA, predominantly at CpG sites, regulated by specific enzymes. DNA methylation typically represses gene transcription, especially when present at promoter regions. The cycle is regulated by DNA methyltransferases (DNMT1, DNMT3A, DNMT3B for methylation) and ten-eleven translocation (TET1, TET2, TET3 for demethylation) families, with cofactors such as S-adenosyl methionine (SAM). This process is central to normal development, cellular differentiation, genomic stability, and the suppression of repetitive elements. Alterations in methylation patterns are implicated in diverse diseases including cancers, aging-related diseases, and neurological disorders. Pharmacological targeting of the cycle's enzymes represents a strategy in cancer treatment, but broad manipulation of DNA methylation risks adverse, unpredictable long-term effects.
Inhibition of DNA methyltransferases blocks the addition of methyl groups, leading to reactivation of silenced genes (e.g., tumor suppressor gene re-expression in cancer therapy) Modulation of TET proteins to influence active demethylation
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