A role for Separase in telomere protection

Nature Communications
Francesca CipressaGiovanni Cenci

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.

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Citations

Dec 15, 2016·Journal of Cellular Biochemistry·Ravinder Kumar
Apr 20, 2016·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Francesco Cucco, Antonio Musio
Nov 23, 2017·Nucleic Acids Research·Francesco CuccoAntonio Musio
Nov 22, 2018·Molecular Biology of the Cell·Benjamin M Stormo, Donald T Fox
Nov 11, 2019·Journal of Medical Genetics·Patrizia SarogniAntonio Musio
Dec 15, 2019·Cell Death & Disease·Giuseppe BossoGiovanni Cenci
Nov 12, 2016·Molecular Biology and Evolution·Yuh Chwen G LeeMia T Levine
Aug 14, 2020·Cells·Silvia Meyer-NavaViviana Valadez-Graham
Jan 13, 2021·Nature Reviews. Cancer·Anand VasudevanJason M Sheltzer
Feb 18, 2018·Current Opinion in Structural Biology·Shukun Luo, Liang Tong
Feb 9, 2021·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kinyo OnYasuko Kato

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Methods Mentioned

BETA
immunoprecipitation
ChIP
transgenic
enzyme-linked immunosorbent assay
pulldown
transfection
transfections
PCR
electrophoresis

Software Mentioned

Quantity One
ImageJ

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