Characterising the Role of the Smc5/6 Complex at Telomeres

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dc.contributor.advisorBeattie, Tara L.
dc.contributor.authorMcLaren, William David John
dc.contributor.committeememberZaremberg, Vanina
dc.contributor.committeememberRiabowol, Karl T.
dc.date2021-06
dc.date.accessioned2021-02-17T19:25:31Z
dc.date.available2021-02-17T19:25:31Z
dc.date.issued2021-01-29
dc.description.abstractSmc5/6 is a member of the SMC family of proteins alongside cohesin and condensin. The complex has previously described roles in DNA repair and more recently a role in telomere binding and maintenance. Here, I demonstrate novel genetic interactions between the Smc5/6 complex and a nuclear pore complex protein Nup170. Both Nup170 and Esc1 have previously been shown to be necessary for telomere maintenance and these two proteins form a complex alongside Sir4, a well-defined regulator of heterochromatin at the telomeres. Loss of Nup170 when combined with a DNA binding-defective mutant of Nse3, a core component of the Smc5/6 complex, leads to increases in subtelomeric gene expression and loss of telomere clustering. It was observed that by combining a deletion mutant of Nup170 with an Nse3 mutant leads to a decrease in survival when exposed to the DNA damage inducing agent MMS as well as an increase in subtelomeric gene expression. Observing Rap1GFP clusters as a readout for telomere clustering shows no change between nse3-1 single mutant and the nup170Δ/nse3-1 double mutant. This indicates that both Smc5/6 and Nup170 operate together to maintain normal telomere function and that they operate in the same pathway to cluster telomeres. These findings help to further elucidate the role of the Smc5/6 complex in maintaining telomere clustering, suppressing expression of subtelomeric genes at telomeres and interactions with Nup170.en_US
dc.identifier.citationMcLaren, W. D. J. (2021). Characterising the Role of the Smc5/6 Complex at Telomeres (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/38644
dc.identifier.urihttp://hdl.handle.net/1880/113097
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
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.en_US
dc.subject.classificationGeneticsen_US
dc.subject.classificationBiochemistryen_US
dc.titleCharacterising the Role of the Smc5/6 Complex at Telomeresen_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Biochemistry and Molecular Biologyen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrueen_US
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