A role for Separase in telomere protection

Francesca Cipressa, Patrizia Morciano, Giuseppe Bosso, Linda Mannini, Alessandra Galati, Grazia Daniela Raffa, Stefano Cacchione, Antonio Musio and Giovanni Cenci ()
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Francesca Cipressa: SAPIENZA University of Rome
Patrizia Morciano: SAPIENZA University of Rome
Giuseppe Bosso: SAPIENZA University of Rome
Linda Mannini: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche
Alessandra Galati: SAPIENZA University of Rome
Grazia Daniela Raffa: SAPIENZA University of Rome
Stefano Cacchione: SAPIENZA University of Rome
Antonio Musio: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche
Giovanni Cenci: SAPIENZA University of Rome

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract Drosophila telomeres are elongated by transposition of specialized retroelements rather than telomerase activity and are assembled independently of the sequence. Fly telomeres are protected by the terminin complex that localizes and functions exclusively at telomeres and by non-terminin proteins that do not serve telomere-specific functions. We show that mutations in the Drosophila Separase encoding gene Sse lead not only to endoreduplication but also telomeric fusions (TFs), suggesting a role for Sse in telomere capping. We demonstrate that Separase binds terminin proteins and HP1, and that it is enriched at telomeres. Furthermore, we show that loss of Sse strongly reduces HP1 levels, and that HP1 overexpression in Sse mutants suppresses TFs, suggesting that TFs are caused by a HP1 diminution. Finally, we find that siRNA-induced depletion of ESPL1, the Sse human orthologue, causes telomere dysfunction and HP1 level reduction in primary fibroblasts, highlighting a conserved role of Separase in telomere protection.

Date: 2016
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DOI: 10.1038/ncomms10405

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