Are poly(ADP-ribosyl)ation by PARP-1 and deacetylation by Sir2 linked?

Jie Zhang

Research output: Contribution to journalArticle

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) safeguards genomic integrity by limiting sister chromatid exchanges. Overstimulation of PARP-1 by extensive DNA damage, however, can result in cell death, as prolonged PARP-1 activation depletes NAD+, a substrate, and elevates nicotinamide, a product. The decline of NAD+ and the rise of nicotinamide may downregulate the activity of Sir2, the NAD+-dependent deacetylases, because deacetylation by Sir2 is dependent on high concentration of NAD+ and inhibited by physiologic level of nicotinamide. The Sir2 deacetylase family has been implicated in mediating gene silencing, longevity and genome stability. It is conceivable that poly(ADP-ribosyl)ation by PARP-1, which is induced by DNA damage, could modulate protein deacetylation by Sir2 via the NAD+/ nicotinamide connection. The possible linkage of the two ancient pathways that mediate broad biological activities may spell profound evolutionary roles for the conserved PARP-1 and Sir2gene families in multicellular eukaryotes.

Original languageEnglish (US)
Pages (from-to)808-814
Number of pages7
JournalBioEssays
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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NAD ADP-ribosyltransferase
Poly(ADP-ribose) Polymerases
nicotinamide
Niacinamide
NAD
Adenosine Diphosphate
DNA damage
DNA Damage
Genes
Sister Chromatid Exchange
Genomic Instability
crossing over
DNA
Gene Silencing
gene silencing
Cell death
Bioactivity
Eukaryota
linkage (genetics)
eukaryotic cells

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Biochemistry
  • Cell Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Agricultural and Biological Sciences (miscellaneous)
  • Plant Science

Cite this

Are poly(ADP-ribosyl)ation by PARP-1 and deacetylation by Sir2 linked? / Zhang, Jie.

In: BioEssays, Vol. 25, No. 8, 01.08.2003, p. 808-814.

Research output: Contribution to journalArticle

Zhang, Jie. / Are poly(ADP-ribosyl)ation by PARP-1 and deacetylation by Sir2 linked?. In: BioEssays. 2003 ; Vol. 25, No. 8. pp. 808-814.
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