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
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Comment
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Diphosphate Ribose / metabolism
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Amino Acid Sequence
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Animals
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Ankyrins / chemistry
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Benzamides / pharmacology
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Catalytic Domain
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DNA / metabolism
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / metabolism*
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Enzyme Inhibitors / pharmacology
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Fluorescent Antibody Technique, Indirect
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Humans
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Molecular Sequence Data
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NAD / metabolism
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Poly(ADP-ribose) Polymerase Inhibitors
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Poly(ADP-ribose) Polymerases / chemistry*
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Poly(ADP-ribose) Polymerases / genetics
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Poly(ADP-ribose) Polymerases / metabolism*
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Protein Structure, Secondary
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Repetitive Sequences, Amino Acid
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Sequence Alignment
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Sequence Homology, Amino Acid
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Tankyrases*
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Telomere / chemistry
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Telomere / enzymology*
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Telomeric Repeat Binding Protein 1
Substances
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Ankyrins
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Benzamides
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DNA-Binding Proteins
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Enzyme Inhibitors
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Poly(ADP-ribose) Polymerase Inhibitors
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Recombinant Proteins
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Telomeric Repeat Binding Protein 1
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NAD
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Adenosine Diphosphate Ribose
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3-aminobenzamide
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DNA
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Poly(ADP-ribose) Polymerases
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Tankyrases
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TNKS protein, human
Associated data
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GENBANK/AF082556
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GENBANK/AF082557
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GENBANK/AF082558
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GENBANK/AF082559