Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-5279
Beneke, S; Cohausz, O; Malanga, M; Boukamp, P; Althaus, F R; Bürkle, A (2008). Rapid regulation of telomere length is mediated by poly(ADP-ribose) polymerase-1. Nucleic Acids Research, 36(19):6309-6317.
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Shelterin/telosome is a multi-protein complex at mammalian telomeres, anchored to the double-stranded region by the telomeric-repeat binding factors-1 and -2. In vitro modification of these proteins by poly(ADP-ribosyl)ation through poly(ADP-ribose) polymerases-5 (tankyrases) and -1/-2, respectively, impairs binding. Thereafter, at least telomeric-repeat binding factor-1 is degraded by the proteasome. We show that pharmacological inhibition of poly(ADP-ribose) polymerase activity in cells from two different species leads to rapid decrease in median telomere length and stabilization at a lower setting. Specific knockdown of poly(ADP-ribose) polymerase-1 by RNA interference had the same effect. The length of the single-stranded telomeric overhang as well as telomerase activity were not affected. Release of inhibition led to a fast re-gain in telomere length to control levels in cells expressing active telomerase. We conclude that poly(ADP-ribose) polymerase-1 activity and probably its interplay with telomeric-repeat binding factor-2 is an important determinant in telomere regulation. Our findings reinforce the link between poly(ADP-ribosyl)ation and aging/longevity and also impact on the use of poly(ADP-ribose) polymerase inhibitors in tumor therapy.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||05 Vetsuisse Faculty > Institute of Veterinary Pharmacology and Toxicology|
|DDC:||570 Life sciences; biology|
|Deposited On:||05 Dec 2008 16:41|
|Last Modified:||27 Nov 2013 18:26|
|Publisher:||Oxford University Press|
|Funders:||Swiss National Science Foundation|
|Additional Information:||Full final text Oxford Journal|
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