NON-THEMATIC REVIEW

Cancer and Metastasis Reviews

, Volume 27, Issue 2, pp 315-334

Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development

  • Samir Kumar PatraAffiliated withCancer Epigenetics Research Email author 
  • , Aditi PatraAffiliated withCancer Epigenetics ResearchVenkateshwara Hatcheries
  • , Federica RizziAffiliated withDepartment of Medicina Sperimentale, University of ParmaIstituto Nazionale Biostrutture e Biosistemi (INBB)
  • , Tapash Chandra GhoshAffiliated withBioinformatics Centre, Bose Institute
  • , Saverio BettuzziAffiliated withDepartment of Medicina Sperimentale, University of ParmaIstituto Nazionale Biostrutture e Biosistemi (INBB)

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Abstract

Cancer cells and tissues exhibit genome wide hypomethylation and regional hypermethylation. CpG-methylation of DNA (MeCpG-DNA) is defined as the formation of a C–C covalent bond between the 5′-C of cytosine and the –CH3 group of S-adenosylmethionine. Removal of the sole –CH3 group from the methylated cytosine of DNA is one of the many ways of DNA-demethylation, which contributes to activation of transcription. The mechanism of demethylation, the candidate enzyme(s) exhibiting direct demethylase activity and associated cofactors are not firmly established. Genome-wide hypomethylation can be obtained in several ways by inactivation of DNMT enzyme activity, including covalent trapping of DNMT by cytosine base analogues. Removal of methyl layer could also be occurred by excision of the 5-methyl cytosine base by DNA glycosylases. The importance of truly chemically defined direct demethylation of intact DNA in regulation of gene expression, development, cell differentiation and transformation are discussed in this contribution.

Keywords

Cancer-epigenetics –CpG– islands (Cytosine-5C-methyl)-DNA-demethylation MBD2 DNA-demethylase Transcription