Characterising the Role of the Smc5/6 Complex at Telomeres

Date
2021-01-29
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Abstract
Smc5/6 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.
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Citation
McLaren, 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.