Maintenance methyltransferase

Stancheva, L, Hensey, C., and Meehan, R.R., Loss of the maintenance methyltransferase, xDnmtl, induces apoptosis in Xenopus embryos, FA7BO J., 20 (8), 1963-1973, 2001. 

Ach, acetylcholine CNS, central nervous system CD, carbidopa COMT, catechol-O-methyltransferase D1, a class of dopamine receptors which includes D, and D5 subtypes D2, a class of dopamine receptors which includes D2, D3, and D4 subtypes DA, dopamine LD, levodopa MAO, monoamine oxidase MD, maintenance dose NMDA, N-methyl-D-aspartate. 

Dervieux, T., Medard, Y., Verpillat, P., et al. (2001) Possible implication of thiopurine S-methyltransferase in occurrence of infectious episodes during maintenance therapy for childhood lymphoblastic leukemia with mercaptopurine. Leukemia. 15, 1706-1712. 

Fig. 1.43. The methylation of DNA 5-methyl-cytidine and maintenance methylation. a) The methylation of cytidine residues on DNA is catalyzed by a methyl transferase that employs S-ade-nosine methionine as a methyl group donor. The peferable substrate for the methyl transferase are hemi-methylated CpG sequences. 5-aza-cytidine is a specific inhibitor of methyl transferses. b) The methylation pattern of DNA remains intact upon DNA replication and is passed on to the daughter cells. The newly synthesized strands are unmethylated immediately after DNA rephca-tion. The methyltransferase uses the previously methylated parent strand as a matrix to methylate the CpG sequences of the newly synthesized strand.

Azathioprine and 6-MP are important agents in the induction and maintenance of remission of ulcerative colitis and Crohn s disease. Although the optimal dose is uncertain, most patients with normal thiopurine-S-methyltransferase (TPMT) activity (see below) are treated with 6-MP, 1-1.5 mg/kg/d, or azathioprine, 2-2.5 mg/kg/d. After 3-6 months of treatment, 50-60% of patients with active disease achieve remission. These agents help maintain remission in up to 80% of patients. Among patients who depend on long-term glucocorticoid therapy to control active disease, purine analogs allow dose reduction or elimination of steroids in the majority. 

Pradhan S, Bacolla A, Wells RD, Roberts RJ. Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem 1999 274 33002-33010. 

Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S. Co-operation and communication between the human maintenance and de novo DNA (c)4osine-5) methyltransferases. EMBO J. 2002 21 4183-4195. 

A characteristic distribution pattern of 5-methyl cytidine (m5C) is found within each cell, which remains intact upon cell division. Mechanisms must therefore exist to ensure that the methylation pattern is precisely retained in the daughter cells following cell division. The enzymes responsible for DNA methylation at CpG sequences are the DNA methyltransferases. The methyl group is derived from S-adenosyl methionine. Several DNA methyltransferases have been characterized, some of which, e.g., Dnmtl, can perform hemi-methylation in the CpG sequences (Fig. 1.38). The preferential substrates for hemi-methylation are DNA sequences in which the complementary strand is already methylated. Such a hemi-methylation occurs, for example, shortly after replication of the sequence. This type of DNA methylation is also called maintenance methylation and is responsible for the inheritance of the methylation pattern. In addition to maintenance methylation, de novo methylation at CpG sequences is also possible. An important inhibitor of DNA methyltransferases is 5-aza-cytidine, which blocks DNA methylation leading to a change in DNA methylation patterns of cells. 

Mermelstein LD, Papoutsakis ET (1993a) Evaluation of macrolide and lincosamide antibiotics for plasmid maintenance in low pH Clostridium acetobutylicum ATCC 824 fermentations. FEMS Microbiol Lett 113 71-76 Mermelstein LD, Papoutsakis ET (1993b) In vivo methylation in Escherichia coli by the Bacillus subtilis phage 3 TI methyltransferase to protect plasmids from restriction upon transformation of Clostridium acetobutylicum ATCC 824. Appl Environ Microbiol 59 1077-1081... 

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