title: Smc5/6 Is a Telomere-Associated Complex that Regulates Sir4 Binding and TPE.
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.
authors: Departments of Biochemistry & Molecular Biology and Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors: Sarah
authors: 0000-0002-5611-2680
authors: S
authors: Moradi-Fard
authors: Departments of Biochemistry & Molecular Biology and Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors: Jessica
authors: J
authors: Sarthi
authors: Departments of Biochemistry & Molecular Biology and Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors: Mireille
authors: M
authors: Tittel-Elmer
authors: Département de Biochimie, Université de Montréal, Montréal, Quebec, Canada.
authors: Maxime
authors: 0000-0002-0495-8967
authors: M
authors: Lalonde
authors: Département de Biochimie, Université de Montréal, Montréal, Quebec, Canada.
authors: Emilio
authors: 0000-0002-7683-8542
authors: E
authors: Cusanelli
authors: Département de Biochimie, Université de Montréal, Montréal, Quebec, Canada.
authors: Pascal
authors: P
authors: Chartrand
authors: Departments of Biochemistry & Molecular Biology and Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors: Jennifer A
authors: JA
authors: Cobb
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D058207:Sumoylation / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics; D014158:Transcription, Genetic; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D034501:Telomere-Binding Proteins; D000097722:Cohesins; C105362:RIF2 protein, S cerevisiae; C061573:SIR4 protein, S cerevisiae; C486627:SMC5 protein, S cerevisiae; C486631:SMC6 protein, S cerevisiae; C108312:condensin complexes