title: The RNA accordion model for template positioning by telomerase RNA during telomeric DNA synthesis.
abstract: Telomerase is a ribonucleoprotein (RNP) enzyme that maintains the ends of linear eukaryotic chromosomes and whose activation is a hallmark of 90% of all cancers. This RNP minimally contains a reverse transcriptase protein subunit (TERT) that catalyzes telomeric DNA synthesis and an RNA subunit (TER) that has templating, architectural and protein-scaffolding roles. Telomerase is unique among polymerases in that it synthesizes multiple copies of the template on the 3' end of a primer following a single binding event, a process known as repeat addition processivity (RAP). Using biochemical assays and single-molecule Förster resonance energy transfer (smFRET) experiments on Tetrahymena thermophila telomerase, we now directly demonstrate that TER contributes to template positioning within the active site and to the template translocation required for RAP. We propose that the single-stranded RNA elements flanking the template act as a molecular accordion, undergoing reciprocal extension and compaction during telomerase translocation.
authors.affiliation: Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Berman
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Akiyama
authors.forename: Michael D
authors.initials: MD
authors.lastname: Stone
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cech
mesh_terms: D016054:DNA, Protozoan / Q000096:biosynthesis* / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D009690:Nucleic Acid Conformation; D012313:RNA / Q000502:physiology*; D016053:RNA, Protozoan / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D019098:Telomerase / Q000502:physiology*; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016808:Tetrahymena thermophila / Q000235:genetics
chemical_list: D016054:DNA, Protozoan; D016053:RNA, Protozoan; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase
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