title: The telomere protein Taz1 is required to prevent and repair genomic DNA breaks.
abstract: One fundamental function of telomeres is to prevent the ends of chromosomes from being sensed and treated as DNA damage. Here we present evidence for additional roles of telomeres in promoting proper chromosome segregation and DNA repair. We find that the fission yeast telomere protein Taz1p is required for cell cycle progression at 20 degrees C, a temperature at which taz1Delta cells exhibit a G(2)/M DNA damage checkpoint delay, chromosome missegregation, and DNA double-strand breaks (DSBs). Spindle assembly checkpoint components and a checkpoint-independent function of Rad3p are required for taz1Delta cells to survive at 20 degrees C. Disruption of topoisomerase II activity suppresses the cold sensitivity of taz1Delta cells, suggesting a scenario in which telomeric entanglement is the primary defect. Furthermore, hypersensitivity to treatments that induce DSBs suggests that Taz1p is involved in DSB repair. Our observations imply roles for Taz1p-containing telomeres in preventing and repairing DNA breaks throughout the genome.
authors.affiliation: Telomere Biology Laboratory, Cancer Research UK, 44 Lincoln's Inn Fields, WC2A 3PX, London, United Kingdom.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Miller
authors.forename: Julia Promisel
authors.initials: JP
authors.lastname: Cooper
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D064447:Checkpoint Kinase 2; D003080:Cold Temperature; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D016195:G2 Phase; D005800:Genes, Fungal; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins; D034501:Telomere-Binding Proteins; C104344:taz1 protein, S pombe; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C456840:rad3 protein, S pombe