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

• Published in: PLoS genetics 2016-08, Vol.12 (8), p.e1006268-e1006268
• Main Authors: Moradi-Fard, Sarah, Sarthi, Jessica, Tittel-Elmer, Mireille, Lalonde, Maxime, Cusanelli, Emilio, Chartrand, Pascal, Cobb, Jennifer A
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Biology and Life Sciences; Cell cycle; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; Chromosomes - genetics; Cohesins; DNA Replication - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Experiments; Gene mutation; Gene silencing; Genes; Identification and classification; Medical research; Melanoma; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Mutation; Observations; Properties; Proteins; Research and Analysis Methods; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Silent Information Regulator Proteins, Saccharomyces cerevisiae - genetics; Silent Information Regulator Proteins, Saccharomyces cerevisiae - metabolism; Sumoylation - genetics; Telomerase; Telomere - genetics; Telomere-Binding Proteins - genetics; Telomeres; Transcription, Genetic
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006268

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.