title: The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae.
abstract: In Saccharomyces cerevisiae and in humans, the telomerase RNA subunit is bound by Ku, a ring-shaped protein heterodimer best known for its function in DNA repair. Ku binding to yeast telomerase RNA promotes telomere lengthening and telomerase recruitment to telomeres, but how this is achieved remains unknown. Using telomere-length analysis and chromatin immunoprecipitation, we show that Sir4 - a previously identified Ku-binding protein that is a component of telomeric silent chromatin - is required for Ku-mediated telomere lengthening and telomerase recruitment. We also find that specifically tethering Sir4 directly to Ku-binding-defective telomerase RNA restores otherwise-shortened telomeres to wild-type length. These findings suggest that Sir4 is the telomere-bound target of Ku-mediated telomerase recruitment and provide one mechanism for how the Sir4-competing Rif1 and Rif2 proteins negatively regulate telomere length in yeast.
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, United States.
authors.forename: Evan P
authors.initials: EP
authors.lastname: Hass
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, United States.
authors.forename: David C
authors.identifier: http://orcid.org/0000-0001-8242-3493
authors.initials: DC
authors.lastname: Zappulla
mesh_terms: D047369:Chromatin Immunoprecipitation; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; C061573:SIR4 protein, S cerevisiae; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D019098:Telomerase
keywords: Ku; S. cerevisiae; chromosomes; genes; telomerase; telomere; transcriptional silencing; yeast