Towards a pharmacology of DNA methylation.
DNA methylation plays an important role in controlling gene-expression programs. Increasing evidence indicates that the enzyme responsible for replicating the DNA methylation pattern, DNA methyltransferase 1 (DNMT1), has a role in cancer. In this article, it is suggested that DNMT1 is a multifunctional protein that has regulatory activities in addition to DNA methylation activity. These functions are assembled into one protein to ensure the coordinate replication of DNA and its methylation pattern. The regulatory activities of DNMT1 are proposed to be involved in cellular transformation and should, therefore, serve as the targets for novel anti-cancer agents.
Szyf
M
M
Dept of Pharmacology and Therapeutics, McGill University, PQ, Montreal, Canada H3G 1Y6. mszyf@pharma.mcgill.ca
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D010090:Oxidoreductases, O-Demethylating / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D010090:Oxidoreductases, O-Demethylating; C117595:methyl-CpG DNA demethylase; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human