The DNA Methylation Machinery as a Therapeutic Target

Moshe      Szyf

doi:10.2174/1389450003349362

Abstract

Pharmacology and therapeutics have traditionally focused on altering the activity of specific proteins that play an important physiological role either to counteract disease processes or to achieve changes in physiology that are of benefit to the patient. The explossion in our understanding of gene expression programs opens up new horizons for pharmacological intervention. Key processes reversibly controlling genetic programs are attractive drug targets. DNA methylation is a fundamental feature of genomes and the control of their function and is therefore a candidate for pharmacological manipulation that might have important therapeutic advantage. This review argues that DNA methylation plays an important role in the control of genomic processes, suggests how the DNA methylation machinery is involved in cancer, identifies the enzymatic processes that are a target for drug intervention, proposes potential therapeutic utilities for agents that manipulate the DNA methylation machinery and discusses nov el drugs that target the DNA methylation machinery

Keywords: DNA Methylation, DNA Demethylases, CIS, Trans, DNA replication, Oncogenic signals, Cell arrest, Tumor suppressor Genes, Normal replication, Cellular Transformation