Polyamines, DNA methylation and cell differentiation. 1988

O Heby, and L Persson, and S S Smith
Department of Zoophysiology, University of Lund, Sweden.

The cellular concentration of AdoMet is normally very much higher than that of dcAdoMet, the aminopropyl group donor in polyamine synthesis. However, when cells are depleted of their putrescine and spermidine, i.e. the aminopropyl group acceptors, the dcAdoMet concentration increases dramatically, to a level that may greatly exceed that of AdoMet. Using a highly purified DNA methyltransferase and its preferred substrates, a defined hemimethylated duplex oligodeoxynucleotide or poly(dI-dC)-poly(dI-dC), we demonstrate that dcAdoMet is a poor methyl group donor, and that it starts to inhibit DNA methylation when its concentration exceeds that of AdoMet. At a dcAdoMet/AdoMet ratio of 5:1 there is very little methyl transfer. This study suggests that the antiproliferative and differentiative effects brought about by inhibitors of polyamine synthesis may be partly attributable to dcAdoMet-mediated inhibition of DNA methylation.

UI MeSH Term Description Entries
D008745 Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed) Methylations
D011073 Polyamines Amine compounds that consist of carbon chains or rings containing two or more primary amino groups. Polyamine
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA

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