The Roles of the Smc5/6 Complex in Heterochromatin Maintenance at Telomeres

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atmire.migration.oldid4606
dc.contributor.advisorCobb, Jennifer
dc.contributor.authorMoradi Fard, Sareh
dc.contributor.committeememberRiabowol, Karl
dc.contributor.committeememberZaremberg, Vanina
dc.contributor.committeememberBeattie, Tara
dc.date.accessioned2016-07-07T15:18:10Z
dc.date.available2016-07-07T15:18:10Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractSMC proteins constitute the core members of the Smc5/6, cohesin and condensin complexes. I 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. Shorter telomeres in nse3-1 cells correlate with a loss of Est2 association to telomeres. Nse3 interacts physically and genetically with two Rap1-binding factors, Rif2 and Sir4. When nse3-1 is combined with rif2Δ, there is a partial reversion in telomere elongation resulting from the loss of RIF2 that is independent of homologous recombination (HR). Shortening of telomeres by nse3-1 appears to be specific to rif2Δ and not a general function towards long telomeres as telomere length of nse3-1/rif1Δ cells is indistinguishable from telomere length in rif1Δ cells. Using genetic approaches, I also find that nse3-1 epistatically relates to positive regulators of telomerase, Tel1 and YKu70. 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 noncoding telomeric repeat-containing RNA (TERRA). SIR4 recovery at telomeres is reduced in cells lacking Smc5/6 functionality and vice versa. However, nse3-1/sir4Δ double mutants show additive defects for telomere shortening and TERRA regulation 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 go beyond its canonical role(s) in HR-mediated events during replication and telomere elongation.en_US
dc.identifier.citationMoradi Fard, S. (2016). The Roles of the Smc5/6 Complex in Heterochromatin Maintenance at Telomeres (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28371en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/28371
dc.identifier.urihttp://hdl.handle.net/11023/3108
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectBiology--Cell
dc.subjectGenetics
dc.subjectBiology--Molecular
dc.subjectBiochemistry
dc.subject.classificationS. cerevisiaeen_US
dc.subject.classificationTelomereen_US
dc.subject.classificationSir4en_US
dc.subject.classificationSmc5/6en_US
dc.subject.classificationRif2en_US
dc.subject.classificationSilencingen_US
dc.subject.classificationHeterochromatinen_US
dc.titleThe Roles of the Smc5/6 Complex in Heterochromatin Maintenance at Telomeres
dc.typedoctoral thesis
thesis.degree.disciplineMedical Science
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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