title: A role for Separase in telomere protection.
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.
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin" Section of Genetics, SAPIENZA University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, Viale Regina Elena 291, 00185 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cipressa
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin" Section of Genetics, SAPIENZA University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, Viale Regina Elena 291, 00185 Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Morciano
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin" Section of Genetics, SAPIENZA University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, Viale Regina Elena 291, 00185 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bosso
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, c/o Area di Ricerca di S. Cataldo Via G. Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Mannini
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin" Section of Genetics, SAPIENZA University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, Viale Regina Elena 291, 00185 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galati
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin" Section of Genetics, SAPIENZA University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, Viale Regina Elena 291, 00185 Rome, Italy.
authors.forename: Grazia Daniela
authors.initials: GD
authors.lastname: Raffa
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin" Section of Genetics, SAPIENZA University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, Viale Regina Elena 291, 00185 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cacchione
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, c/o Area di Ricerca di S. Cataldo Via G. Moruzzi 1, 56124 Pisa, Italy.|Istituto Toscano Tumori, Via T. Alderotti 26N, 50139 Firenze, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Musio
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin" Section of Genetics, SAPIENZA University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, Viale Regina Elena 291, 00185 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cenci
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D064247:Separase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C452193:heterochromatin protein 1, Drosophila; C083046:terminin; C577987:ESPL1 protein, human; D064247:Separase