title: Tankyrase, a poly(ADP-ribose) polymerase at human telomeres.
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.
authors.affiliation: The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: I
authors.initials: I
authors.lastname: Giriat
authors.forename: A
authors.initials: A
authors.lastname: Schmitt
authors.forename: T
authors.initials: T
authors.lastname: de Lange
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000737:chemistry; D001549:Benzamides / Q000494:pharmacology; D020134:Catalytic Domain; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D038501:Tankyrases; D016615:Telomere / Q000737:chemistry / Q000201:enzymology*; D035321:Telomeric Repeat Binding Protein 1
chemical_list: D000246:Adenosine Diphosphate Ribose; D017487:Ankyrins; D001549:Benzamides; D004247:DNA; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009243:NAD; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D011994:Recombinant Proteins; D038501:Tankyrases; D035321:Telomeric Repeat Binding Protein 1; C025160:3-aminobenzamide; C418109:TNKS protein, human