Abstract
Budding yeast telomeres are reversibly bound at the nuclear envelope through two partially redundant pathways that involve the Sir2/3/4 silencing complex and the Yku70/80 heterodimer1,2. To better understand how this is regulated, we studied the role of SUMOylation in telomere anchoring. We find that the PIAS-like SUMO E3 ligase Siz2 sumoylates both Yku70/80 and Sir4 in vivo and promotes telomere anchoring to the nuclear envelope. Remarkably, loss of Siz2 also provokes telomere extension in a telomerase-dependent manner that is epistatic with loss of the helicase Pif1. Consistent with our previously documented role for telomerase in anchorage3, normal telomere anchoring in siz2 Δ is restored by PIF1 deletion. By live-cell imaging of a critically short telomere, we show that telomeres shift away from the nuclear envelope when elongating. We propose that SUMO-dependent association with the nuclear periphery restrains bound telomerase, whereas active elongation correlates with telomere release.
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Acknowledgements
We thank V. Zakian and E. Johnson for yeast strains, and N. Iglesias and M. Arneric for advice on the single-telomere extension system. H.C.F. was financially supported by Marie Curie and EMBO long-term fellowships, and the Gasser Laboratory by the Novartis Research Foundation. J.L. was supported by the Swiss National Science Foundation, the European Community’s Seventh Framework Programme (grant 200950) and a European Research Council advanced investigator grant (grant 232812). Both laboratories are part of the SNF-funded Frontiers in Genetics National Center of Competence in Research.
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S.M.G. and J.L. directed the study. H.C.F. did the biochemical experiments and with the help of V.K. carried out all telomere localization and minimal anchor experiments. B.L. did most of the telomere length assays and H.S. did the short-telomere mating assay. The manuscript was prepared by H.C.F. and S.M.G. with contributions from J.L., B.L. and H.S.
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Ferreira, H., Luke, B., Schober, H. et al. The PIAS homologue Siz2 regulates perinuclear telomere position and telomerase activity in budding yeast. Nat Cell Biol 13, 867–874 (2011). https://doi.org/10.1038/ncb2263
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DOI: https://doi.org/10.1038/ncb2263
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