TANKYRASE, A POLY(ADP-RIBOSE) POLYMERASE AT HUMAN TELOMERES

Tankyrase, a protein with homology to ankyrins and to the catalytic do main of poly(adenosine diphosphate-ribose) polymerase (PARP), was iden tified and localized to human telomeres. Tankyrase binds to the telome ric protein TRF1 (telomeric repeat binding factor-1), a negative regul ator of telomere Length maintenance. Like ankyrins, tankyrase contains 24 ankyrin repeats in a domain responsible for its interaction with T RF1. Recombinant tankyrase was found to have PARP activity in vitro, w ith both TRF1 and tankyrase functioning as accepters for adenosine dip hosphate (ADP)-ribosylation. ADP-ribosylation of TRF1 diminished its a bility to bind to telomeric DNA in vitro, suggesting that telomere fun ction in human cells is regulated by poly(ADP-ribosyl)ation.