The evolutionarily conserved factor Sus1/ENY2 plays a role in telomere length maintenance
Por:
A. GALAN, E. GARCIA-OLIVER, C. NUNO-CABANES, L. RUBINSTEIN, M. KUPIEC and S. RODRIGUEZ-NAVARRO
Publicada:
1 jun 2018
Resumen:
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 sem1 Delta, esc2 Delta and rsc2 Delta, which cause telomere shortening. We find that rsc2 Delta (short telomeres) have reduced levels of mono-ubiquitinated histone H2B at lysine 123 (H2BK123ub(1)), whereas sus1 Delta mutants or double-mutants sus1 Delta rsc2 Delta exhibit longer telomeres and higher H2BK123ub(1) 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.
Filiaciones:
:
CIPF, Gene Express & RNA Metab Lab, CE Primo Yufera 3, Valencia 46012, Spain
E. GARCIA-OLIVER:
CIPF, Gene Express & RNA Metab Lab, CE Primo Yufera 3, Valencia 46012, Spain
:
CIPF, Gene Express & RNA Metab Lab, CE Primo Yufera 3, Valencia 46012, Spain
CSIC, Inst Biomed Valencia, Gene Express & RNA Metab Lab, C Jaime Roig 11, Valencia 46010, Spain
L. RUBINSTEIN:
Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel
M. KUPIEC:
Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel
:
CIPF, Gene Express & RNA Metab Lab, CE Primo Yufera 3, Valencia 46012, Spain
CSIC, Inst Biomed Valencia, Gene Express & RNA Metab Lab, C Jaime Roig 11, Valencia 46010, Spain
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