Cancer and Metastasis Reviews

, Volume 27, Issue 2, pp 315–334 | Cite as

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

  • Samir Kumar Patra
  • Aditi Patra
  • Federica Rizzi
  • Tapash Chandra Ghosh
  • Saverio Bettuzzi
NON-THEMATIC REVIEW

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 

Notes

Acknowledgements

The work was done in part at the McGill University, Montreal, Canada, during one of the authors (SKP) stay as academic trainee staff, supported by a fellowship from the National Cancer Institute of Canada (NCIC); and also done in part at the University of California at San Francisco, USA, during the stay of SKP and AP as postdoctoral scientists supported by fellowships from NIH, and thereafter from NCIRE, California, USA. Grant support for SB: ABO Project 2006, Venezia, Italy; AICR (UK) Grant No. 06-711; Istituto Nazionale Biostrutture e Biosistemi (INBB), Roma; Associazione Assistenza Tumori Alto Adige—Südtiroler Krebshilfe, Bolzano (Bozen), Italy. We apologize to those, whose work and related publications we have not been able to discuss and cite due to space limitations.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Samir Kumar Patra
    • 1
  • Aditi Patra
    • 1
    • 2
  • Federica Rizzi
    • 3
    • 4
  • Tapash Chandra Ghosh
    • 5
  • Saverio Bettuzzi
    • 3
    • 4
  1. 1.Cancer Epigenetics ResearchNadiaIndia
  2. 2.Venkateshwara HatcheriesSalt Lake CityIndia
  3. 3.Department of Medicina SperimentaleUniversity of ParmaParmaItaly
  4. 4.Istituto Nazionale Biostrutture e Biosistemi (INBB)RomeItaly
  5. 5.Bioinformatics CentreBose InstituteKolkataIndia

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