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The PIAS homologue Siz2 regulates perinuclear telomere position and telomerase activity in budding yeast

Nature Cell Biology volume 13, pages 867–874 (2011)Cite this article

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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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Figure 1: Yeast telomeres are delocalized by deletion of SIZ2.
Figure 2: Siz2-dependent SUMOylation of Sir4 and Yku70/80 promotes chromatin anchoring.
Figure 3: SUMO modification of Yku70 and Yku80 enhances telomere anchoring.
Figure 4: Pif1 links Siz2-dependent telomere length and localization regulation.
Figure 5: Critically short telomeres detach from the periphery on elongation during the first S phase.

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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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Author notes

  1. Brian Luke

    Present address: Present address: ZMBH-Universität Heidelberg, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany,

  2. Heiko Schober

    Present address: Present address: Institute of Cell Biology, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland,

Authors and Affiliations

  1. Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland

    Helder C. Ferreira, Heiko Schober, Véronique Kalck & Susan M. Gasser

  2. Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland

    Brian Luke & Joachim Lingner

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Contributions

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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Correspondence to Susan M. Gasser.

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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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