title: Taz1, Rap1 and Rif1 act both interdependently and independently to maintain telomeres.
abstract: Telomere protection and maintenance are accomplished through the coordinated actions of telomere-specific DNA binding proteins and their interacting partners. The fission yeast ortholog of human TRF1/2, Taz1, binds telomeric DNA and regulates numerous aspects of telomere function. Here, we ask which aspects of Taz1 function are mediated through its interacting proteins, Rap1 and Rif1. We demonstrate that rap1+ deletion phenocopies some, but not all, aspects of taz1Delta telomere dysfunction, while Rif1 exhibits a very different functional spectrum. Rap1 acts in a Taz1-dependent pathway to prevent chromosome end fusions and regulate telomeric 3' overhang formation, while Rif1 is dispensable for these functions. Telomerase inhibition by Taz1 is mediated by two separate pathways, one involving Rap1 and the other involving Rif1. In contrast, Taz1 is uniquely required to prevent chromosomal entanglements and missegregation at cold temperatures. Strikingly, while rap1+ deletion exacerbates the cold sensitivity of taz1Delta cells, rif1+ deletion restores full viability. Thus, Rap1 and Rif1 are each required for a subset of the functions of Taz1, but each acquires Taz1-independent functions in its absence. Furthermore, Taz1 can function independently of its known binding partners.
authors.affiliation: Cancer Research UK, London Research Institute, London, UK.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Miller
authors.forename: Miguel Godinho
authors.initials: MG
authors.lastname: Ferreira
authors.forename: Julia Promisel
authors.initials: JP
authors.lastname: Cooper
mesh_terms: D002470:Cell Survival; D015825:Chromosomes, Fungal / Q000235:genetics; D009154:Mutation; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000502:physiology*; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; C104344:taz1 protein, S pombe