The Role of Epigenetic Events in Cancer Essay Example | Topics and Well Written Essays - 1000 words

The Role of Epigenetic Events in Cancer - Essay Example It is worth mentioning that most CpG sites have been lost from mammalian genomes during evolution, but in about 1% of human DNA consists of short areas where CpG sites have escaped depletion. Repetitive sequences of the human genome contain approximately 50% of all CpGs. Similar values are expected for other mammalian genomes. In contrast to CpG islands repetitive elements are thought to be constantly methylated. DNA methylation of most repetitive elements is maintained throughout development and even maintained during germ cell development. Methylated cytosines are more prone to fixate mutations compared with cytosine, C to T transitions occur frequently at methylated CpGs within repetitive elements. In consequence, this leads to an overall depletion of CpGs in repetitive elements and hence the bulk genome and an overall CpG deficit in mammalian genomes. CpG dinucleotide sequences are frequently the target of a chemical modification known as DNA methylation. The covalent modificatio n of the cytosine ring by a family of enzymes called DNA methyltransferases converts cytosines that are located 5 to guanosines to 5-methylcytosine. 5-methylcytosine has a propensity to undergo deamination to become uracil, which in turn becomes a thymidine during the next round of DNA replication if the deaminated base has not been repaired. The resulting C to T transition is mirrored by a corresponding G to A transition on the complementary DNA strand. As a result of methylation and subsequent deamination, CpG dinucleotide sequences have been progressively lost from the human genome over the course of many generations. Thus, the hypermutability of CpG sequences has led to a relative paucity of CpG sites in the human genome. The CpG dinucleotides that are the targets of DNA methyltransferases are distributed asymmetrically throughout the genome. Most regions of the genome have been depleted of CpG sites by spontaneous deamination.