Cell cycle dependent localization of the telomeric PARP, tankyrase, to nuclear pore complexes and centrosomes

Tankyrase is a human poly(ADP-ribose) polymerase that was initially identif ied through its interaction with the telomeric protein TRF1, a negative reg ulator of telomere length. In vitro poly(ADP-ribosyl)ation by tankyrase inh ibits TRF1 binding to telomeric DNA suggesting a role for tankyrase in telo mere function. We previously demonstrated that tankyrase co-localizes with TRF1 at the ends of human chromosomes in metaphase, Here we show that tanky rase localizes to additional subcellular sites in a cell cycle dependent ma nner. In interphase, tankyrase colocalized with TRF1 to telomeres, but in a ddition was found to reside at nuclear pore complexes, as evidenced by indi rect immunofluorescence, subcellular fractionation and immunoelectron micro scopy, At mitosis, concomitant with nuclear envelope breakdown and nuclear pore complex disassembly, tankyrase was found to relocate around the perice ntriolar 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, perha ps by TRF1, Indeed, localization of exogenously-expressed tankyrase to telo meres was dependent upon co-transfection with TRF1. These data indicate tha t the subcellular localization of tankyrase can be regulated by both the ce ll cycle and TRF1.