Initial Phase of Epigenetic Pathways in Carcinogenesis and Mutagenesis

Abstract

Epigenetic pathway is one of the major routes to carcinogenesis. A key enzyme involved in this pathway is DNA-MTase (DMT). There are evidences that carcinogens cause an increase in the activity of this enzyme. The increased activity is due to an increase in transcriptional control of the three forms of the enzyme, Dnm1, Dnm3a and Dnm3b [1]. The general function of DMTs was described by Berletch et al. [2]. The enzyme catalyses the transfer of methyl groups from 5adenoxylmethionine (SAM) to GpC islands in key protein binding sites of DNA. The essential function of DMTs is to methylate the CpG islands in cancer suppressor genes, thus inactivating these suppressor genes and enabling the expression of cancer associated genes and thereby allowing the carcinogenic process to occur [3-5]. In normal cells, most CpG sequences are methylated but there are still 15% of which are not methylated, the CpG sequences are clustered in 20,000 regions called CpG islands which are not methylated. Aberrant methylation leads to cancer [5]. That is DMT is the key that opens the door to a major pathway leading to cancer.