Browsing by Author "Moradi Fard, Sareh"

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    The Roles of the Smc5/6 Complex in Heterochromatin Maintenance at Telomeres
    (2016) Moradi Fard, Sareh; Cobb, Jennifer; Riabowol, Karl; Zaremberg, Vanina; Beattie, Tara
    SMC 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.