title: Multi-step coordination of telomerase recruitment in fission yeast through two coupled telomere-telomerase interfaces.
abstract: Tightly controlled recruitment of telomerase, a low-abundance enzyme, to telomeres is essential for regulated telomere synthesis. Recent studies in human cells revealed that a patch of amino acids in the shelterin component TPP1, called the TEL-patch, is essential for recruiting telomerase to telomeres. However, how TEL-patch-telomerase interaction integrates into the overall orchestration of telomerase regulation at telomeres is unclear. In fission yeast, Tel1(ATM)/Rad3(ATR)-mediated phosphorylation of shelterin component Ccq1 during late S phase is involved in telomerase recruitment through promoting the binding of Ccq1 to a telomerase accessory protein Est1. Here, we identify the TEL-patch in Tpz1(TPP1), mutations of which lead to decreased telomeric association of telomerase, similar to the phosphorylation-defective Ccq1. Furthermore, we find that telomerase action at telomeres requires formation and resolution of an intermediate state, in which the cell cycle-dependent Ccq1-Est1 interaction is coupled to the TEL-patch-Trt1 interaction, to achieve temporally regulated telomerase elongation of telomeres.
authors.affiliation: Department of Biological Chemistry, University of California, Irvine School of Medicine, Irvine, United States.
authors.forename: Xichan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Biological Chemistry, University of California, Irvine School of Medicine, Irvine, United States.
authors.forename: Jinqiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Biological Chemistry, University of California, Irvine School of Medicine, Irvine, United States.
authors.forename: Hyun-Ik
authors.initials: HI
authors.lastname: Jun
authors.affiliation: Department of Biological Chemistry, University of California, Irvine School of Medicine, Irvine, United States.
authors.forename: Jin-Kwang
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Biological Chemistry, University of California, Irvine School of Medicine, Irvine, United States.
authors.forename: Feng
authors.identifier: 0000-0002-1704-7257
authors.initials: F
authors.lastname: Qiao
mesh_terms: D000595:Amino Acid Sequence; D002453:Cell Cycle; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009708:Nucleotidases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017385:Sequence Homology; D000089804:Shelterin Complex; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins
chemical_list: C495876:ACD protein, human; C529647:Ccq1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C456840:rad3 protein, S pombe; C513624:tel1 protein, S pombe; C569590:EST1 protein, S pombe; D019098:Telomerase; D009708:Nucleotidases; C039170:deoxynucleotide 3'-phosphatase
keywords: DNA replication; S. pombe; cell cycle; chromosomes; genes; recruitment; telomerase; telomeres