Cologne Seminars on Ageing "Regulation of Replicative Senescence and Protein Stability by Tankyrase"

About Dr. Smith's talk:

Tankyrase 1 and 2 are enzymes that regulate both telomere dynamics and protein stability through ADP-ribosylation. At telomeres, tankyrase is normally recruited by the binding protein TRF1 to resolve sister telomere cohesion during mitosis, ensuring proper chromosome separation. However, in aged cells with shortened telomeres, this recruitment is inefficient, leading to persistent cohesion between sister telomeres. This cohesion is maintained by RNA–DNA hybrid structures known as R-loops, which, somewhat unexpectedly, play a protective role by delaying the onset of replicative senescence when present at higher levels. In addition to its telomeric role, tankyrase is tightly regulated by posttranslational modifications that control its stability. Typically, tankyrase-mediated poly-ADP-ribose chains are recognized by the E3 ubiquitin ligase RNF146, which targets tankyrase and its binding partners for degradation. However, a newly identified modification—ubiquitylation of ADP-ribose on serine residues—blocks the formation of these poly-ADP-ribose chains, preventing RNF146 binding and thereby stabilizing tankyrase and associated proteins. This reveals a complex interplay between ADP-ribosylation and ubiquitination in regulating protein turnover and suggests that such mechanisms may also influence tankyrase function at telomeres.

This event is aimed at a specialist audience.