The evolutionarily conserved factor Sus1/ENY2 plays a role in telomere length maintenance

Amparo Galán, Encar García-Oliver, Carme Nuño-Cabanes, Linda Rubinstein, Martin Kupiec, Susana Rodríguez-Navarro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Sus1 is a conserved protein involved in histone H2B de-ubiquitination and mRNA export from the nucleus in eukaryotes. Previous studies implicated Sus1 partners in genome integrity including telomere homeostasis. However, the implication of Sus1 in telomere maintenance remains largely unknown. In this study, we found that yeast Sus1 interacts physically and genetically with factors involved in telomere maintenance and its absence leads to elongated telomeres. Deletion of several of Sus1’s partners also leads to longer telomeres. Our results rule out a direct role for Sus1 in recruiting telomerase subunits to telomeres. However, we observe that deletion of SUS1 leads to elongated telomeres even in the presence of mutations like sem1Δ, esc2Δ and rsc2Δ, which cause telomere shortening. We find that rsc2Δ (short telomeres) have reduced levels of mono-ubiquitinated histone H2B at lysine 123 (H2BK123ub1), whereas sus1Δ mutants or double-mutants sus1Δ rsc2Δ exhibit longer telomeres and higher H2BK123ub1 levels. These results suggest that Sus1 activity as a H2B de-ubiquitination modulator plays a role in negatively regulating telomere length. Our results provide solid evidence for a role of Sus1 in negatively regulating telomere length through the modulation of H2BK123 mono-ubiquitination and its interaction with the nuclear pore complex.

Original languageEnglish
Pages (from-to)635-644
Number of pages10
JournalCurrent Genetics
Volume64
Issue number3
DOIs
StatePublished - 1 Jun 2018

Funding

FundersFunder number
Generalitat Valenciana of Spain
Israel Cancer Research Foundation
Israel Science Fund
Israel Cancer Research Fund
Princeton UniversityLKG239
Federación Española de Enfermedades Raras
Ministerio de Economía y CompetitividadBFU2014-57636-P, BFU2011-23418
Generalitat ValencianaACOMP/2015/096, PROMETEO/2016/093, ACOMP/2014/061
European Regional Development Fund

    Keywords

    • H2B de-ubiquitination
    • RSC
    • SAGA
    • Sus1
    • TREX-2
    • Telomere length

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