SMC proteins constitute the core members of the Smc5/6, cohesin and condensin complexes. We demonstrate that Smc5/6 is present at telomeres throughout the cell cycle and its association with chromosome ends is dependent on Nse3, a subcomponent of the complex. Cells harboring a temperature sensitive mutant, nse3-1, are defective in Smc5/6 localization to telomeres and have slightly shorter telomeres. Nse3 interacts physically and genetically with two Rap1-binding factors, Rif2 and Sir4. Reduction in telomere-associated Smc5/6 leads to defects in telomere clustering, dispersion of the silencing factor, Sir4, and a loss in transcriptional repression for sub-telomeric genes and non-coding telomeric repeat-containing RNA (TERRA). SIR4 recovery at telomeres is reduced in cells lacking Smc5/6 functionality and vice versa. However, nse3-1/ sir4 Δ double mutants show additive defects for telomere shortening and TPE indicating the contribution of Smc5/6 to telomere homeostasis is only in partial overlap with SIR factor silencing. These findings support a role for Smc5/6 in telomere maintenance that is separate from its canonical role(s) in HR-mediated events during replication and telomere elongation.

Smc5/6 Is a Telomere-Associated Complex that Regulates Sir4 Binding and TPE / Moradi Fard, Sarah; Sarthi, Jessica; Tittel Elmer, Mireille; Lalonde, Maxime; Cusanelli, Emilio; Chartrand, Pascal; Cobb, Jennifer A.. - In: PLOS GENETICS. - ISSN 1553-7404. - 12:8(2016), pp. e1006268.1-e1006268.22. [10.1371/journal.pgen.1006268]

Smc5/6 Is a Telomere-Associated Complex that Regulates Sir4 Binding and TPE

Cusanelli, Emilio;
2016-01-01

Abstract

SMC proteins constitute the core members of the Smc5/6, cohesin and condensin complexes. We demonstrate that Smc5/6 is present at telomeres throughout the cell cycle and its association with chromosome ends is dependent on Nse3, a subcomponent of the complex. Cells harboring a temperature sensitive mutant, nse3-1, are defective in Smc5/6 localization to telomeres and have slightly shorter telomeres. Nse3 interacts physically and genetically with two Rap1-binding factors, Rif2 and Sir4. Reduction in telomere-associated Smc5/6 leads to defects in telomere clustering, dispersion of the silencing factor, Sir4, and a loss in transcriptional repression for sub-telomeric genes and non-coding telomeric repeat-containing RNA (TERRA). SIR4 recovery at telomeres is reduced in cells lacking Smc5/6 functionality and vice versa. However, nse3-1/ sir4 Δ double mutants show additive defects for telomere shortening and TPE indicating the contribution of Smc5/6 to telomere homeostasis is only in partial overlap with SIR factor silencing. These findings support a role for Smc5/6 in telomere maintenance that is separate from its canonical role(s) in HR-mediated events during replication and telomere elongation.
2016
8
Moradi Fard, Sarah; Sarthi, Jessica; Tittel Elmer, Mireille; Lalonde, Maxime; Cusanelli, Emilio; Chartrand, Pascal; Cobb, Jennifer A.
Smc5/6 Is a Telomere-Associated Complex that Regulates Sir4 Binding and TPE / Moradi Fard, Sarah; Sarthi, Jessica; Tittel Elmer, Mireille; Lalonde, Maxime; Cusanelli, Emilio; Chartrand, Pascal; Cobb, Jennifer A.. - In: PLOS GENETICS. - ISSN 1553-7404. - 12:8(2016), pp. e1006268.1-e1006268.22. [10.1371/journal.pgen.1006268]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/148991
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