Effect of DNA-binding drugs on the activity of DNA methylase from Ehrlich's ascites tumour cells

Abstract

DNA methylase from Ehrlich's ascites tumour cells preferentially methylates DNA with high GC content. The methylase activity was not affected by the presence of the oligonucleotides, dCdG or dCdCdGdG, which are known to be part of the methyl-acceptor sequence for mammalian DNA methylase. DNA from 5-azacytidine-treated ascites cells was a good methyl acceptor. Actinomycin D, ethydium bromide and quinacrine inhibited the methylase activity. Distamycin A also inhibited the methylation of DNA from 5-azacytidine-treated ascites cells, but did not inhibit the methylation of (dG,dC)n. The inhibitory effect of all these drugs was overcome by increasing the DNA concentration. Non-competitive type inhibition in regard to S-adenosylmethionine was observed with all the DNA-binding drugs.