title: Cell cycle dependent localization of the telomeric PARP, tankyrase, to nuclear pore complexes and centrosomes.
abstract: Tankyrase is a human poly(ADP-ribose) polymerase that was initially identified through its interaction with the telomeric protein TRF1, a negative regulator of telomere length. In vitro poly(ADP-ribosyl)ation by tankyrase inhibits TRF1 binding to telomeric DNA suggesting a role for tankyrase in telomere function. We previously demonstrated that tankyrase co-localizes with TRF1 at the ends of human chromosomes in metaphase. Here we show that tankyrase localizes to additional subcellular sites in a cell cycle dependent manner. In interphase, tankyrase co-localized with TRF1 to telomeres, but in addition was found to reside at nuclear pore complexes, as evidenced by indirect immunofluorescence, subcellular fractionation and immunoelectron microscopy. At mitosis, concomitant with nuclear envelope breakdown and nuclear pore complex disassembly, tankyrase was found to relocate around the pericentriolar matrix of mitotic centrosomes. This complex staining pattern along with the observation that tankyrase did not contain a nuclear localization signal suggested that its telomeric localization might be regulated, perhaps by TRF1. Indeed, localization of exogenously-expressed tankyrase to telomeres was dependent upon co-transfection with TRF1. These data indicate that the subcellular localization of tankyrase can be regulated by both the cell cycle and TRF1.
authors.affiliation: Laboratory for Cell Biology and Genetics, The Rockefeller University, New York NY 10021, USA.
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: T
authors.initials: T
authors.lastname: de Lange
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D018385:Centrosome / Q000737:chemistry* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008854:Microscopy, Electron; D008938:Mitosis / Q000235:genetics*; D009685:Nuclear Envelope / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D038501:Tankyrases; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D035321:Telomeric Repeat Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D011065:Poly(ADP-ribose) Polymerases; D038501:Tankyrases; D035321:Telomeric Repeat Binding Protein 1; C418109:TNKS protein, human