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Inhibition of Poly(ADP-Ribosyl)ation Allows DNA Hypermethylation

  • Anna Reale
  • Giuseppe Zardo
  • Maria Malanga
  • Jordanka Zlatanova
  • Paola Caiafa
Chapter
  • 912 Downloads
Part of the Medical Intelligence Unit book series (MIUN)

Abstract

This chapter emphasizes that along the chain of events that induce DNA methylation-dependent chromatin condensation, a post-synthetic modification other than histone acetylation, poly(ADP-ribosyl)ation, participates in the establishment and maintenance of methylation-free regions of chromatin. In fact, several lines of in vitro and in vivo evidence have shown that poly(ADP-ribosyl)ation is involved in the control of DNA methylation pattern, protecting genomic DNA from full methylation. More recent studies have provided some clues to the understanding of the molecular mechanism(s) connecting poly(ADP-ribosyl)ation with DNA methylation. We aim here to demonstrate the direct correlation existing between inhibition of poly(ADP-ribose) polymerases and DNA hypermethylation, and to describe some possible mechanisms underlying this molecular link. We will then present our hypothesis that the inhibition of the poly(ADP-ribosyl)ation process in the cell may be responsible for the anomalous hypermethylation of oncosuppressor gene promoters during tumorigenesis and to suggest the possibility that an active poly(ADP-ribosyl)ation process is also involved in maintaining the unmethylated state of CpG islands in normal cells.

Keywords

Methylation Pattern Chromatin Fiber Linker Histone Demethylase Activity Full Methylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Eurekah.com and Kluwer Academic/Plenum Publishers 2005

Authors and Affiliations

  • Anna Reale
    • 1
  • Giuseppe Zardo
    • 1
  • Maria Malanga
    • 2
  • Jordanka Zlatanova
    • 3
  • Paola Caiafa
    • 1
  1. 1.Department of Cellular Biotechnologies and HaematologyUniversite di Roma “La Sapienza”RomeItaly
  2. 2.Department of Biological ChemistryUniversity “Federico II” of NaplesNaplesItaly
  3. 3.Department of Chemistry and Chemical EngineeringPolytechnic UniversityBrooklynUSA

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