Tankyrase, a poly(ADP-ribose) polymerase at human telomeres

Science. 1998 Nov 20;282(5393):1484-7. doi: 10.1126/science.282.5393.1484.

Abstract

Tankyrase, a protein with homology to ankyrins and to the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP), was identified and localized to human telomeres. Tankyrase binds to the telomeric protein TRF1 (telomeric repeat binding factor-1), a negative regulator of telomere length maintenance. Like ankyrins, tankyrase contains 24 ankyrin repeats in a domain responsible for its interaction with TRF1. Recombinant tankyrase was found to have PARP activity in vitro, with both TRF1 and tankyrase functioning as acceptors for adenosine diphosphate (ADP)-ribosylation. ADP-ribosylation of TRF1 diminished its ability to bind to telomeric DNA in vitro, suggesting that telomere function in human cells is regulated by poly(ADP-ribosyl)ation.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Amino Acid Sequence
  • Animals
  • Ankyrins / chemistry
  • Benzamides / pharmacology
  • Catalytic Domain
  • DNA / metabolism
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Molecular Sequence Data
  • NAD / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / chemistry*
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Repetitive Sequences, Amino Acid
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Tankyrases*
  • Telomere / chemistry
  • Telomere / enzymology*
  • Telomeric Repeat Binding Protein 1

Substances

  • Ankyrins
  • Benzamides
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Recombinant Proteins
  • Telomeric Repeat Binding Protein 1
  • NAD
  • Adenosine Diphosphate Ribose
  • 3-aminobenzamide
  • DNA
  • Poly(ADP-ribose) Polymerases
  • Tankyrases
  • TNKS protein, human

Associated data

  • GENBANK/AF082556
  • GENBANK/AF082557
  • GENBANK/AF082558
  • GENBANK/AF082559