Inhibition of DNA methyltransferase inhibits DNA replication

Ectopic expression of DNA methyltransferase transforms vertebrate cells, an d inhibition of DNA methyltransferase reverses the transformed phenotype by an unknown mechanism. me tested the hypothesis that the presence of an act ive DNA methyltransferase is required for DNA replication in human non-smal l cell lung carcinoma A549 cells. We show that the inhibition of DNA methyl transferase by two novel mechanisms negatively affects DNA synthesis and pr ogression through the cell cycle, Competitive polymerase chain reaction of newly synthesized DNA shows decreased origin activity at three previously c haracterized origins of replication following DNA methyltransferase inhibit ion. We suggest that the requirement of an active DNA methyltransferase for the functioning of the replication machinery has evolved to coordinate DNA replication and inheritance of the DNA methylation pattern.