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

Authors

    • Cancer Epigenetics Research
  • Aditi Patra
    • Cancer Epigenetics Research
    • Venkateshwara Hatcheries
  • Federica Rizzi
    • Department of Medicina SperimentaleUniversity of Parma
    • Istituto Nazionale Biostrutture e Biosistemi (INBB)
  • Tapash Chandra Ghosh
    • Bioinformatics CentreBose Institute
  • Saverio Bettuzzi
    • Department of Medicina SperimentaleUniversity of Parma
    • Istituto Nazionale Biostrutture e Biosistemi (INBB)
NON-THEMATIC REVIEW

DOI: 10.1007/s10555-008-9118-y

Cite this article as:
Patra, S.K., Patra, A., Rizzi, F. et al. Cancer Metastasis Rev (2008) 27: 315. doi:10.1007/s10555-008-9118-y

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-demethylationMBD2DNA-demethylaseTranscription

Copyright information

© Springer Science+Business Media, LLC 2008