T R Cech

Summary

Affiliation: University of Colorado
Country: USA

Publications

  1. ncbi request reprint On the occasion of the 25th anniversary of the discovery of catalytic RNA
    Thomas R Cech
    Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
    Biol Chem 388:661-2. 2007
  2. ncbi request reprint The noncoding RNA revolution-trashing old rules to forge new ones
    Thomas R Cech
    Howard Hughes Medical Institute Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, USA Electronic address
    Cell 157:77-94. 2014
  3. pmc DNA-induced dimerization of the single-stranded DNA binding telomeric protein Pot1 from Schizosaccharomyces pombe
    Jayakrishnan Nandakumar
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 0215, USA
    Nucleic Acids Res 40:235-44. 2012
  4. pmc Many disease-associated variants of hTERT retain high telomerase enzymatic activity
    Arthur J Zaug
    Department of Chemistry and Biochemistry, University of Colorado Biofrontiers Institute, Boulder, CO 80309 0596, USA, Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 0596, USA and Department of Chemistry and Biochemistry, DePauw University, Greencastle, IN 46135, USA
    Nucleic Acids Res 41:8969-78. 2013
  5. pmc The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity
    Jayakrishnan Nandakumar
    University of Colorado Biofrontiers Institute, Boulder, Colorado 80309, USA
    Nature 492:285-9. 2012
  6. pmc The RNA accordion model for template positioning by telomerase RNA during telomeric DNA synthesis
    Andrea J Berman
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado, USA
    Nat Struct Mol Biol 18:1371-5. 2011
  7. pmc 3' terminal diversity of MRP RNA and other human noncoding RNAs revealed by deep sequencing
    Katherine C Goldfarb
    Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO, USA
    BMC Mol Biol 14:23. 2013
  8. doi request reprint How a chemist looks at RNA
    Thomas R Cech
    University of Colorado Biofrontiers Institute, Boulder, CO 80309 0596, USA
    Angew Chem Int Ed Engl 52:75-8. 2013
  9. pmc The RNA worlds in context
    Thomas R Cech
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309 0215, USA
    Cold Spring Harb Perspect Biol 4:a006742. 2012
  10. pmc Global expression changes resulting from loss of telomeric DNA in fission yeast
    Jeffrey G Mandell
    Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 0215, USA
    Genome Biol 6:R1. 2005

Collaborators

Detail Information

Publications85

  1. ncbi request reprint On the occasion of the 25th anniversary of the discovery of catalytic RNA
    Thomas R Cech
    Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
    Biol Chem 388:661-2. 2007
  2. ncbi request reprint The noncoding RNA revolution-trashing old rules to forge new ones
    Thomas R Cech
    Howard Hughes Medical Institute Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, USA Electronic address
    Cell 157:77-94. 2014
    ..Many, though not all, ncRNAs exploit the power of base pairing to selectively bind and act on other nucleic acids. Here, we describe the pathway of ncRNA research, where every established "rule" seems destined to be overturned. ..
  3. pmc DNA-induced dimerization of the single-stranded DNA binding telomeric protein Pot1 from Schizosaccharomyces pombe
    Jayakrishnan Nandakumar
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 0215, USA
    Nucleic Acids Res 40:235-44. 2012
    ..We further show that the S. pombe telomeric protein Tpz1, like its mammalian homolog TPP1, increases the affinity of Pot1 for telomeric single-stranded DNA and enhances the discrimination of Pot1 against RNA...
  4. pmc Many disease-associated variants of hTERT retain high telomerase enzymatic activity
    Arthur J Zaug
    Department of Chemistry and Biochemistry, University of Colorado Biofrontiers Institute, Boulder, CO 80309 0596, USA, Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 0596, USA and Department of Chemistry and Biochemistry, DePauw University, Greencastle, IN 46135, USA
    Nucleic Acids Res 41:8969-78. 2013
    ..Alternatively, mutations may perturb functions such as the recruitment of telomerase to telomeres, which are essential in vivo but not revealed by simple enzyme assays. ..
  5. pmc The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity
    Jayakrishnan Nandakumar
    University of Colorado Biofrontiers Institute, Boulder, Colorado 80309, USA
    Nature 492:285-9. 2012
    ..Given that the interaction between telomerase and TPP1 is required for telomerase function in vivo, the TEL patch of TPP1 provides a new target for anticancer drug development...
  6. pmc The RNA accordion model for template positioning by telomerase RNA during telomeric DNA synthesis
    Andrea J Berman
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado, USA
    Nat Struct Mol Biol 18:1371-5. 2011
    ..We propose that the single-stranded RNA elements flanking the template act as a molecular accordion, undergoing reciprocal extension and compaction during telomerase translocation...
  7. pmc 3' terminal diversity of MRP RNA and other human noncoding RNAs revealed by deep sequencing
    Katherine C Goldfarb
    Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, CO, USA
    BMC Mol Biol 14:23. 2013
    ..Here we employ 3' RACE coupled with high-throughput sequencing to characterize the 3' terminal sequences of human MRP RNA and other noncoding RNAs that form RNP complexes...
  8. doi request reprint How a chemist looks at RNA
    Thomas R Cech
    University of Colorado Biofrontiers Institute, Boulder, CO 80309 0596, USA
    Angew Chem Int Ed Engl 52:75-8. 2013
    ....
  9. pmc The RNA worlds in context
    Thomas R Cech
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309 0215, USA
    Cold Spring Harb Perspect Biol 4:a006742. 2012
    ..The fun comes when we try to use our secure knowledge of the modern RNA world to infer what the primordial RNA world might have looked like...
  10. pmc Global expression changes resulting from loss of telomeric DNA in fission yeast
    Jeffrey G Mandell
    Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 0215, USA
    Genome Biol 6:R1. 2005
    ..Survivors with linear chromosomes have normal growth rates and morphology, but those with circular chromosomes have growth defects and are enlarged. We report the global gene-expression response of S. pombe to loss of trt1+...
  11. doi request reprint Evolution of biological catalysis: ribozyme to RNP enzyme
    T R Cech
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Cold Spring Harb Symp Quant Biol 74:11-6. 2009
    ..Recent findings support the argument that RNP enzymes are not undergoing extinction, but instead, they are continuing to evolve and to elaborate new functions...
  12. ncbi request reprint Beginning to understand the end of the chromosome
    Thomas R Cech
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
    Cell 116:273-9. 2004
    ..The roles of telomerase in both cellular immortality and cancer are vibrant areas of current research...
  13. ncbi request reprint Ribozymes, the first 20 years
    T R Cech
    Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815 6789, USA
    Biochem Soc Trans 30:1162-6. 2002
    ....
  14. ncbi request reprint Structural biology. The ribosome is a ribozyme
    T R Cech
    Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815 6789, USA
    Science 289:878-9. 2000
    ..Nissen et al., Muth et al.)...
  15. doi request reprint Crawling out of the RNA world
    Thomas R Cech
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
    Cell 136:599-602. 2009
    ..Furthermore, the RNA components of RNP enzymes show no evidence of fading out but instead, in some cases, have elaborated new functions...
  16. pmc Modulation of telomerase activity by telomere DNA-binding proteins in Oxytricha
    S J Froelich-Ammon
    Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309 0215, USA
    Genes Dev 12:1504-14. 1998
    ..We conclude that the telomere protein inhibits telomerase by rendering the telomeric DNA inaccessible, thereby helping to maintain telomere length...
  17. ncbi request reprint Telomerase catalytic subunit homologs from fission yeast and human
    T M Nakamura
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    Science 277:955-9. 1997
    ..Thus, the proposed telomerase catalytic subunits are phylogenetically conserved and represent a deep branch in the evolution of reverse transcriptases...
  18. ncbi request reprint Pot1, the putative telomere end-binding protein in fission yeast and humans
    P Baumann
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
    Science 292:1171-5. 2001
    ..It now appears that the protein that caps the ends of chromosomes is widely dispersed throughout the eukaryotic kingdom...
  19. ncbi request reprint RNA tertiary folding monitored by fluorescence of covalently attached pyrene
    S K Silverman
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado at Boulder 80309 0215, USA
    Biochemistry 38:14224-37. 1999
    ....
  20. pmc Three Ever Shorter Telomere (EST) genes are dispensable for in vitro yeast telomerase activity
    J Lingner
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    Proc Natl Acad Sci U S A 94:11190-5. 1997
    ....
  21. ncbi request reprint Energetics and cooperativity of tertiary hydrogen bonds in RNA structure
    S K Silverman
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado at Boulder 80309 0215, USA
    Biochemistry 38:8691-702. 1999
    ..4 to -0.5 kcal/mol per tertiary hydrogen bond may be more generally applicable to RNA folding...
  22. ncbi request reprint Reverse transcriptase motifs in the catalytic subunit of telomerase
    J Lingner
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    Science 276:561-7. 1997
    ..Thus, the reverse transcriptase protein fold, previously known to be involved in retroviral replication and retrotransposition, is essential for normal chromosome telomere replication in diverse eukaryotes...
  23. pmc Quantifying the energetic interplay of RNA tertiary and secondary structure interactions
    S K Silverman
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado at Boulder, 80309 0215, USA
    RNA 5:1665-74. 1999
    ..This tertiary/secondary interplay is likely relevant to the folding of many large RNA and to bimolecular snRNA-snRNA and snRNA-intron RNA interactions...
  24. ncbi request reprint A preorganized active site in the crystal structure of the Tetrahymena ribozyme
    B L Golden
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    Science 282:259-64. 1998
    ..The binding pockets for both the 5' splice site helix and guanosine are formed and oriented in the absence of these substrates. Thus, this large ribozyme is largely preorganized for catalysis, much like a globular protein enzyme...
  25. ncbi request reprint Multiple folding pathways for the P4-P6 RNA domain
    S K Silverman
    Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado at Boulder, Boulder, Colorado 80309, USA
    Biochemistry 39:12465-75. 2000
    ..The fast kinetic phase reflects folding that is facilitated by these interactions, whereas the slow kinetics are observed when these interactions are disrupted at lower ionic strength and higher temperature...
  26. pmc Protection of telomeres by the Ku protein in fission yeast
    P Baumann
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309, USA
    Mol Biol Cell 11:3265-75. 2000
    ..The conclusion that nonhomologous end-joining is not required for chromosome circularization was further supported by analysis of survivors in strains lacking the genes for both trt1(+) and lig4(+)...
  27. ncbi request reprint Two modes of survival of fission yeast without telomerase
    T M Nakamura
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    Science 282:493-6. 1998
    ..Moreover, the massive elongation of telomeres in taz1- cells is absent in the double mutant. Thus, Taz1p appears to regulate telomeric recombination as well as telomerase activity in fission yeast...
  28. ncbi request reprint Telomerase is a true reverse transcriptase. A review
    T R Cech
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder 80309 0215, USA
    Biochemistry (Mosc) 62:1202-5. 1997
    ..We find it remarkable that the same type of protein structure required for retroviral replication is now seen to be essential for normal chromosome telomere replication in diverse eukaryotes...
  29. pmc Mutagenesis and comparative sequence analysis of a base triple joining the two domains of group I ribozymes
    M A Tanner
    Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309 0215, USA
    RNA 3:1037-51. 1997
    ..Repositioning of the base triple to form a new set of interactions may be required for the second step of splicing...
  30. ncbi request reprint RNA as a flexible scaffold for proteins: yeast telomerase and beyond
    D C Zappulla
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA
    Cold Spring Harb Symp Quant Biol 71:217-24. 2006
    ....
  31. ncbi request reprint A stem-loop of Tetrahymena telomerase RNA distant from the template potentiates RNA folding and telomerase activity
    J M Sperger
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA
    Biochemistry 40:7005-16. 2001
    ..Thus an RNA element far from the template makes a major contribution to Tetrahymena telomerase enzyme activity...
  32. ncbi request reprint Expression of a RecQ helicase homolog affects progression through crisis in fission yeast lacking telomerase
    Jeffrey G Mandell
    Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 0215, USA
    J Biol Chem 280:5249-57. 2005
    ..These results strengthen the notion that in multiple organisms RecQ helicases contribute to survival after telomere damage...
  33. pmc Kinetic pathway for folding of the Tetrahymena ribozyme revealed by three UV-inducible crosslinks
    W D Downs
    Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, University of Colorado, Boulder 80309 0215, USA
    RNA 2:718-32. 1996
    ..Specific binding sites for Mg2+ may make this cation particularly efficient at electrostatic stabilization during folding of these ribozyme structures...
  34. ncbi request reprint DNA self-recognition in the structure of Pot1 bound to telomeric single-stranded DNA
    Ming Lei
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Nature 426:198-203. 2003
    ..The structure also explains how Pot1p avoids binding the vast excess of RNA in the nucleus...
  35. pmc Essential functions of amino-terminal domains in the yeast telomerase catalytic subunit revealed by selection for viable mutants
    K L Friedman
    Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309 0215, USA
    Genes Dev 13:2863-74. 1999
    ..A mutant close to the amino terminus retained RNA binding and in vitro enzymatic activity but was defective in vivo, suggesting a role in interaction with other macromolecular components of telomerase...
  36. pmc An early transition state for folding of the P4-P6 RNA domain
    S K Silverman
    Department of Chemistry and Biochemistry, University of Colorado at Boulder, 80309 0215, USA
    RNA 7:161-6. 2001
    ..Our kinetic data are some of the first to provide quantitative values for an activation barrier and location of a transition state for tertiary folding of an RNA domain...
  37. ncbi request reprint Structure of the Tetrahymena ribozyme: base triple sandwich and metal ion at the active site
    Feng Guo
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
    Mol Cell 16:351-62. 2004
    ..Therefore, we provide a picture of how the ribozyme active site positions both a catalytic metal ion and the nucleophilic guanosine for catalysis prior to binding its RNA substrate...
  38. ncbi request reprint Switching human telomerase on and off with hPOT1 protein in vitro
    Ming Lei
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    J Biol Chem 280:20449-56. 2005
    ..Thus, depending on its location relative to the DNA 3'-end, hPOT1 can either inhibit telomerase action or form a preferred substrate for telomerase. We propose that another factor catalyzes the interconversion of these states in vivo...
  39. ncbi request reprint Crystal structure of the essential N-terminal domain of telomerase reverse transcriptase
    Steven A Jacobs
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Nat Struct Mol Biol 13:218-25. 2006
    ..The TEN domain's ability to bind both RNA and telomeric DNA, coupled with the notably strong effects on activity upon mutagenesis of single surface residues, suggest how this domain contributes to telomerase catalysis...
  40. pmc Nuclear proteins that bind the pre-mRNA 3' splice site sequence r(UUAG/G) and the human telomeric DNA sequence d(TTAGGG)n
    F Ishikawa
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309 0215
    Mol Cell Biol 13:4301-10. 1993
    ..These studies establish the binding specificities of these D and E hnRNPs. Furthermore, they suggest the possibility that these hnRNPs could perhaps bind to chromosome telomeres, in addition to having a role in pre-mRNA metabolism...
  41. ncbi request reprint Structural basis of the enhanced stability of a mutant ribozyme domain and a detailed view of RNA--solvent interactions
    K Juneau
    Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
    Structure 9:221-31. 2001
    ..In addition, the higher resolution model provides new details of metal ion-RNA interactions and identifies a core of ordered water molecules that may be integral to RNA tertiary structure formation...
  42. ncbi request reprint Self-splicing and enzymatic activity of an intervening sequence RNA from Tetrahymena
    Thomas R Cech
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    Biosci Rep 24:362-85. 2004
  43. pmc Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro
    Arthur J Zaug
    Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    Proc Natl Acad Sci U S A 102:10864-9. 2005
    ..We propose an additional role for hPOT1 in telomere maintenance: disrupting G-quadruplex structures in telomeric DNA, thereby allowing proper elongation by telomerase...
  44. ncbi request reprint Atomic level architecture of group I introns revealed
    Quentin Vicens
    Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Colorado, UCB 215, Boulder, CO 80309 0215, USA
    Trends Biochem Sci 31:41-51. 2006
    ..Group I intron structures thus provide much awaited and extremely valuable snapshots of how these ribozymes coordinate substrate binding and catalysis...
  45. ncbi request reprint Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection
    Ming Lei
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Nat Struct Mol Biol 11:1223-9. 2004
    ..pombe Pot1pN-ssDNA complex, whereas the second OB fold binds and protects the 3' end of the ssDNA. These results provide an atomic-resolution model for chromosome end-capping...
  46. ncbi request reprint The Euplotes La motif protein p43 has properties of a telomerase-specific subunit
    Stefan Aigner
    Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309 0215, USA
    Biochemistry 42:5736-47. 2003
    ..Thus, p43 joins the telomerase reverse transcriptase and the yeast proteins Est1p and Est3p as the only telomerase-specific proteins identified so far...
  47. pmc Essential regions of Saccharomyces cerevisiae telomerase RNA: separate elements for Est1p and Est2p interaction
    April J Livengood
    Department of MCD Biology, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309 0215, USA
    Mol Cell Biol 22:2366-74. 2002
    ..More generally, our results support a role for the telomerase RNA serving as a scaffold for binding key protein subunits...
  48. pmc Multiple yeast genes, including Paf1 complex genes, affect telomere length via telomerase RNA abundance
    Amy D Mozdy
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Mol Cell Biol 28:4152-61. 2008
    ..This report establishes that a subset of telomere length genes act by modulating telomerase RNA abundance...
  49. pmc In vitro selection of the Naegleria GIR1 ribozyme identifies three base changes that dramatically improve activity
    E Jabri
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder 80309 0215, USA
    RNA 4:1481-92. 1998
    ..Furthermore, the selection for higher activity appeared to select for increased structural stability...
  50. pmc The Cech Symposium: a celebration of 25 years of ribozymes, 10 years of TERT, and 60 years of Tom
    Quentin Vicens
    Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 0215, USA
    RNA 14:397-403. 2008
    ....
  51. pmc Local RNA structural changes induced by crystallization are revealed by SHAPE
    Quentin Vicens
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, Univeristy of Colorado, Boulder, CO 80309 0215, USA
    RNA 13:536-48. 2007
    ....
  52. pmc Triple-helix structure in telomerase RNA contributes to catalysis
    Feng Qiao
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, Campus Box 215, University of Colorado, Boulder, Colorado 80309 0215, USA
    Nat Struct Mol Biol 15:634-40. 2008
    ..The role of RNA in telomerase catalysis may have been acquired relatively recently or, alternatively, telomerase may be a molecular fossil representing an evolutionary link between RNA enzymes and RNP enzymes...
  53. pmc Low abundance of telomerase in yeast: implications for telomerase haploinsufficiency
    Amy D Mozdy
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    RNA 12:1721-37. 2006
    ..Because yeast telomerase is tethered at chromosome ends, the finding that it may be outnumbered by its telomeric DNA substrates provides a new perspective for interpreting the results of telomere maintenance studies...
  54. pmc Comparison of crystal structure interactions and thermodynamics for stabilizing mutations in the Tetrahymena ribozyme
    Feng Guo
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    RNA 12:387-95. 2006
    ....
  55. pmc Mutation in TERT separates processivity from anchor-site function
    Arthur J Zaug
    Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Nat Struct Mol Biol 15:870-2. 2008
    ....
  56. pmc Tetrahymena telomerase protein p65 induces conformational changes throughout telomerase RNA (TER) and rescues telomerase reverse transcriptase and TER assembly mutants
    Andrea J Berman
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Mol Cell Biol 30:4965-76. 2010
    ..Second, p65 acts as a molecular buttress within the assembled RNP, mutually stabilizing TER and TERT in catalytically active conformations...
  57. pmc Yeast telomerase RNA: a flexible scaffold for protein subunits
    David C Zappulla
    Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    Proc Natl Acad Sci U S A 101:10024-9. 2004
    ..In the case of yeast telomerase, we propose that the RNA serves a very different function, providing a flexible tether for the protein subunits...
  58. ncbi request reprint Cooperative binding of single-stranded telomeric DNA by the Pot1 protein of Schizosaccharomyces pombe
    Ming Lei
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Biochemistry 41:14560-8. 2002
    ..Together, the binding properties of Pot1pN suggest that the protein anchors itself at the very 3' end of a chromosome and then fills in very efficiently, coating the entire single-stranded overhang of the telomere...
  59. ncbi request reprint Evolution of Tetrahymena ribozyme mutants with increased structural stability
    Feng Guo
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Nat Struct Biol 9:855-61. 2002
    ..The wild type ribozyme and the selected mutants provide pairs of mesophilic and thermophilic homologs for studying the origin of their thermal stability...
  60. pmc In vivo selection of better self-splicing introns in Escherichia coli: the role of the P1 extension helix of the Tetrahymena intron
    Feng Guo
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309 0215, USA
    RNA 8:647-58. 2002
    ..This study emphasizes the value of using libraries of random mutations to improve the activity of ribozymes in heterologous contexts in vivo...
  61. ncbi request reprint Effects of nucleotide analogues on Euplotes aediculatus telomerase processivity: evidence for product-assisted translocation
    Michael B Jarstfer
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309 0215, USA
    Biochemistry 41:151-61. 2002
    ..The data support a model that includes the formation of an intramolecular secondary structure within the product DNA to facilitate translocation. The most likely structure is a G-G hairpin...
  62. pmc A natural ribozyme with 3',5' RNA ligase activity
    Quentin Vicens
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, UCB 215, Boulder, Colorado 80309 0215, USA
    Nat Chem Biol 5:97-9. 2009
    ..In the process, this ribozyme forms a unique circular RNA that incorporates the exogenous guanosine cofactor added during self-splicing. This finding may have relevance to a prebiotic RNA world and to modern biology...
  63. pmc How telomeric protein POT1 avoids RNA to achieve specificity for single-stranded DNA
    Jayakrishnan Nandakumar
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309 0215, USA
    Proc Natl Acad Sci U S A 107:651-6. 2010
    ..At amino acid 62, Phe discriminates against RNA binding and Tyr allows RNA binding. We further show that TPP1 greatly augments POT1's discrimination against RNA...
  64. pmc Toward predicting self-splicing and protein-facilitated splicing of group I introns
    Quentin Vicens
    Howard Hughes Medical Institute, University of Colorado, Department of Chemistry and Biochemistry, Boulder, Colorado 80309 0215, USA
    RNA 14:2013-29. 2008
    ..Together, correlations between sequence, predicted structure and splicing begin to establish rules that should facilitate our ability to predict the self-splicing activity of any group I intron from its sequence...
  65. pmc Inhibition of yeast telomerase action by the telomeric ssDNA-binding protein, Cdc13p
    David C Zappulla
    Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309, USA
    Nucleic Acids Res 37:354-67. 2009
    ....
  66. pmc Engineering cis-telomerase RNAs that add telomeric repeats to themselves
    Feng Qiao
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, Campus Box 215, University of Colorado, Boulder, CO 80309 0215, USA
    Proc Natl Acad Sci U S A 107:4914-8. 2010
    ..More generally, the cis system will allow structure-function relationships of each RNA molecule to be read directly through the reaction that it performs on itself...
  67. ncbi request reprint A miniature yeast telomerase RNA functions in vivo and reconstitutes activity in vitro
    David C Zappulla
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Nat Struct Mol Biol 12:1072-7. 2005
    ..We find that substitution of Mini-T for wild-type TLC1 in a reconstituted system yields robust activity, allowing the contributions of individual yeast telomerase components to be directly assessed...
  68. pmc A template-proximal RNA paired element contributes to Saccharomyces cerevisiae telomerase activity
    Anita G Seto
    Department of Chemistry and Biochemistry, and Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309 0215, USA
    RNA 9:1323-32. 2003
    ..In addition, the in vitro activity of the paired element mutant indicates that the RNA element has additional functions in enzyme processivity and in directing template usage by telomerase...
  69. pmc Soluble domains of telomerase reverse transcriptase identified by high-throughput screening
    Steven A Jacobs
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    Protein Sci 14:2051-8. 2005
    ..These results provide a tool for future structural and biophysical studies of TERT...
  70. pmc Human Pot1 (protection of telomeres) protein: cytolocalization, gene structure, and alternative splicing
    Peter Baumann
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Mol Cell Biol 22:8079-87. 2002
    ..In addition to these splice variants, the Pot1 family is expanded by the identification of six more genes from diverse species. Pot1-like proteins have now been found in plants, animals, yeasts, and microsporidia...
  71. ncbi request reprint Engineering disulfide cross-links in RNA using thiol-disulfide interchange chemistry
    S B Cohen
    University of Colorado, Boulder, USA
    Curr Protoc Nucleic Acid Chem . 2001
    ..Such motions are believed to be linked to biological function, and the protocols presented in this unit are among the few simple ways to assess such dynamics...
  72. ncbi request reprint Telomerase and the maintenance of chromosome ends
    T M Bryan
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, Campus Box 215, University of Colorado, Boulder, CO 80309 0215, USA
    Curr Opin Cell Biol 11:318-24. 1999
    ..Other proteins that modulate telomerase activity in vivo are also being identified, including a functionally conserved family of proteins with Myb-like DNA-binding domains and proteins that are involved in DNA double-strand break repair...
  73. pmc A bulged stem tethers Est1p to telomerase RNA in budding yeast
    Anita G Seto
    Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
    Genes Dev 16:2800-12. 2002
    ..We propose that this RNA structure links the enzymatic core of telomerase with Est1p, thereby allowing Est1p to recruit or activate telomerase at the telomere...
  74. pmc POT1-TPP1 enhances telomerase processivity by slowing primer dissociation and aiding translocation
    Chrysa M Latrick
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado Boulder, 80309 0215, USA
    EMBO J 29:924-33. 2010
    ..These results support a model in which POT1-TPP1 enhances telomerase processivity in a manner markedly different from the sliding clamps used by DNA polymerases...
  75. pmc The Euplotes telomerase subunit p43 stimulates enzymatic activity and processivity in vitro
    Stefan Aigner
    Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309 0215, USA
    RNA 10:1108-18. 2004
    ..To our knowledge, this represents the first demonstration that an authentic telomerase accessory protein can directly affect the enzymatic activity of the core enzyme in vitro...
  76. ncbi request reprint Sequence-specific and 3'-end selective single-strand DNA binding by the Oxytricha nova telomere end binding protein alpha subunit
    Scott Classen
    Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado 80309 0215, USA
    Biochemistry 42:9269-77. 2003
    ..Comparison of the structural and binding data provides unique insights into the ways in which proteins recognize and bind single-stranded DNA...
  77. pmc Functional interaction between telomere protein TPP1 and telomerase
    Arthur J Zaug
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado, Boulder, 80309, USA
    Genes Dev 24:613-22. 2010
    ..We suggest that a sequence-specific interaction between TPP1 in the TPP1-POT1-telomeric DNA complex and the G100 region of the TEN domain of TERT is necessary for high-processivity telomerase action...
  78. pmc Tetrahymena telomerase is active as a monomer
    Tracy M Bryan
    Children s Medical Research Institute, Westmead, New South Wales 2145, Australia
    Mol Biol Cell 14:4794-804. 2003
    ..We were also unable to detect dimerization of native telomerase from mating and vegetative Tetrahymena cell extracts. These results demonstrate that Tetrahymena telomerase does not need to dimerize to be active and processive...
  79. pmc Yeast telomerase is specialized for C/A-rich RNA templates
    Klaus Forstemann
    Swiss Institute for Experimental Cancer Research ISREC, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nucleic Acids Res 31:1646-55. 2003
    ..Thus, in contrast to retroviral RTs that can reverse transcribe any RNA sequence into DNA, the budding yeast telomerase RT is specialized for its C-rich RNA template...
  80. ncbi request reprint POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates
    Patricia L Opresko
    Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, Maryland 21224, USA
    J Biol Chem 280:32069-80. 2005
    ..We propose roles for the cooperation of POT1 with RecQ helicases WRN and BLM in resolving DNA structures at telomeric ends, in a manner that protects the telomeric 3' tail as it is exposed during unwinding...
  81. ncbi request reprint The chemical repertoire of natural ribozymes
    Jennifer A Doudna
    Department of Molecular and Cell Biology, and Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA
    Nature 418:222-8. 2002
    ..This versatility has lent credence to the idea that RNA molecules may have been central to the early stages of life on Earth...
  82. pmc N-terminal domain of yeast telomerase reverse transcriptase: recruitment of Est3p to the telomerase complex
    Katherine L Friedman
    Vanderbilt University, Department of Biological Sciences, Nashville, Tennessee 37235, USA
    Mol Biol Cell 14:1-13. 2003
    ..We conclude that Est2p region I is required for the recruitment of Est3p to yeast telomerase. Given the phylogenetic conservation of region I of TERT, this protein domain may provide the equivalent function in all telomerases...
  83. ncbi request reprint The POT1-TPP1 telomere complex is a telomerase processivity factor
    Feng Wang
    Department of Biological Chemistry, University of Michigan Medical School, MSRBIII 5301D, 1150 W Medical Center Drive, Ann Arbor, Michigan 48109, USA
    Nature 445:506-10. 2007
    ..We propose that POT1-TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension...
  84. ncbi request reprint Human POT1 facilitates telomere elongation by telomerase
    Lorel M Colgin
    Children s Medical Research Institute, 214 Hawkesbury Road, Westmead, NSW 2145, Australia
    Curr Biol 13:942-6. 2003
    ..hPOT1 was unable to lengthen the telomeres of telomerase-negative cells unless telomerase activity was induced. These data suggest that a normal function of hPOT1 is to facilitate telomere elongation by telomerase...
  85. ncbi request reprint RNA finds a simpler way
    Thomas R Cech
    Nature 428:263-4. 2004