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.

Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells

“…Human Tankyrase 1 (TANK1) that plays a key role in maintaining telomere integrity has a Zn-binding domain in its catalytic site and is therefore dependent on Zn for its function (Lehtio et al 2008). TANK1 is a member of the growing family of (poly ADP-ribose) polymerases (PARPs) that interacts with ADP-ribosylases the telomere-binding protein TRF1 (Smith et al 1998). The role of TANK1 involves displacing TRF1 from telomeric DNA and suggests that TANK1 may be a positive regulator of telomere length in telomerase-expressing cells (Smith and de Lange 2000;van Steensel and de Lange 1997).…”

Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation

“…For example, TRF1 may limit accessibility of telomerase to the telomere despite enhanced expression of hTERT (van Steensel and de Lange, 1998). The inhibitory function of TRF1 could be relieved by overexpression of the recently described ADP-ribosylase Tankyrase (Smith et al, 1998), and it is tempting to speculate that this e ect may be independent of c-Myc.…”

Cancer and aging: the importance of telomeres in genome maintenance

“…TRF1, for example, binds two highly related poly-ADP ribosylases (PARPs), TANK1 and TANK2 [68,69] ( Fig. 3).…”

“…3). Although the TANKs can be found at telomeres, and even ADP-ribosylate TRF1 in vitro [68,70], these proteins reside predominantly in Golgi-type vesicles, and have also been identified at centrosomes [69,[71][72][73]. The precise functions of TANKs are not known.…”