telomerase

Summary

Summary: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-.

Top Publications

  1. pmc Telomeres and telomerase in cancer
    Steven E Artandi
    Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Carcinogenesis 31:9-18. 2010
  2. pmc Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice
    Mariela Jaskelioff
    Belfer Institute for Applied Cancer Science and Departments of Medical Oncology, Medicine and Genetics, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 469:102-6. 2011
  3. ncbi Extension of life-span by introduction of telomerase into normal human cells
    A G Bodnar
    Geron Corporation, Menlo Park, CA 94025, USA
    Science 279:349-52. 1998
  4. doi Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells
    Katrin Hoffmeyer
    Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
    Science 336:1549-54. 2012
  5. pmc TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal
    Patrick J Killela
    Pediatric Brain Tumor Foundation Institute at Duke, and Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 110:6021-6. 2013
  6. pmc Telomere dysfunction induces metabolic and mitochondrial compromise
    Ergun Sahin
    Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 470:359-65. 2011
  7. doi Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins
    Paula Martinez
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro 3, Madrid E 28029, Spain
    Nat Rev Cancer 11:161-76. 2011
  8. pmc Sequence variants at the TERT-CLPTM1L locus associate with many cancer types
    Thorunn Rafnar
    deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
    Nat Genet 41:221-7. 2009
  9. pmc Telomerase modulates Wnt signalling by association with target gene chromatin
    Jae Il Park
    Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 460:66-72. 2009
  10. ncbi Switching and signaling at the telomere
    E H Blackburn
    Department of Biochemistry and Biophysics, University of California, San Francisco, 94143, USA
    Cell 106:661-73. 2001

Detail Information

Publications436 found, 100 shown here

  1. pmc Telomeres and telomerase in cancer
    Steven E Artandi
    Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Carcinogenesis 31:9-18. 2010
    ..In most advanced cancers, telomerase is reactivated and serves to maintain telomere length and emerging data have also documented the capacity of ..
  2. pmc Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice
    Mariela Jaskelioff
    Belfer Institute for Applied Cancer Science and Departments of Medical Oncology, Medicine and Genetics, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 469:102-6. 2011
    ..Such instigators include progressively damaged genomes. Telomerase-deficient mice have served as a model system to study the adverse cellular and organismal consequences of wide-..
  3. ncbi Extension of life-span by introduction of telomerase into normal human cells
    A G Bodnar
    Geron Corporation, Menlo Park, CA 94025, USA
    Science 279:349-52. 1998
    ..To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected ..
  4. doi Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells
    Katrin Hoffmeyer
    Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
    Science 336:1549-54. 2012
    b>Telomerase activity controls telomere length and plays a pivotal role in stem cells, aging, and cancer. Here, we report a molecular link between Wnt/β-catenin signaling and the expression of the telomerase subunit Tert...
  5. pmc TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal
    Patrick J Killela
    Pediatric Brain Tumor Foundation Institute at Duke, and Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 110:6021-6. 2013
    ..associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse ..
  6. pmc Telomere dysfunction induces metabolic and mitochondrial compromise
    Ergun Sahin
    Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 470:359-65. 2011
    ..PGC-1β, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes...
  7. doi Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins
    Paula Martinez
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Melchor Fernandez Almagro 3, Madrid E 28029, Spain
    Nat Rev Cancer 11:161-76. 2011
    ..Telomere elongation is carried out by telomerase. Telomerase can also act as a transcriptional modulator of the Wnt-β-catenin signalling pathway and has RNA-..
  8. pmc Sequence variants at the TERT-CLPTM1L locus associate with many cancer types
    Thorunn Rafnar
    deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
    Nat Genet 41:221-7. 2009
    ..However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.
  9. pmc Telomerase modulates Wnt signalling by association with target gene chromatin
    Jae Il Park
    Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 460:66-72. 2009
    ..Either stimulation of Wnt/beta-catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo, although the mechanisms by which telomerase ..
  10. ncbi Switching and signaling at the telomere
    E H Blackburn
    Department of Biochemistry and Biophysics, University of California, San Francisco, 94143, USA
    Cell 106:661-73. 2001
    ..Also discussed are cellular responses to compromising the functions of telomeres and of telomerase, which synthesizes telomeric DNA.
  11. pmc Human telomerase reverse transcriptase (hTERT) is a novel target of the Wnt/β-catenin pathway in human cancer
    Yong Zhang
    Department of Biochemistry, Yong Loo Lin School of Medicine, 8 Medical Drive, National University of Singapore, 117597 Singapore
    J Biol Chem 287:32494-511. 2012
    b>Telomerase activation plays a critical role in human carcinogenesis through the maintenance of telomeres, but the activation mechanism during carcinogenesis remains unclear...
  12. ncbi A telomerase component is defective in the human disease dyskeratosis congenita
    J R Mitchell
    Department of Molecular and Cell Biology, University of California, Berkeley 94720 3204, USA
    Nature 402:551-5. 1999
    ..Here we show that dyskerin is associated not only with H/ACA small nucleolar RNAs, but also with human telomerase RNA, which contains an H/ACA RNA motif...
  13. pmc Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells
    B Elenbaas
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Genes Dev 15:50-65. 2001
    ..Here we show that introduction of three genes encoding the SV40 large-T antigen, the telomerase catalytic subunit, and an H-Ras oncoprotein into primary HMECs results in cells that form tumors when ..
  14. ncbi Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes
    Neeta S Roy
    Department of Neurology, Weill Medical College of Cornell University, New York, New York 10021, USA
    Nat Med 12:1259-68. 2006
    ..fate, we cocultured HES cells that were exposed to both sonic hedgehog and fibroblast growth factor 8 with telomerase-immortalized human fetal midbrain astrocytes...
  15. ncbi TRF2 protects human telomeres from end-to-end fusions
    B van Steensel
    The Rockefeller University, New York, New York 10021, USA
    Cell 92:401-13. 1998
    ..The results raise the possibility that chromosome end fusions and senescence in primary human cells may be caused by loss by TRF2 from shortened telomeres...
  16. ncbi Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
    S E Artandi
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 406:641-5. 2000
    ..complexes that cap the ends of eukaryotic chromosomes and are maintained by the reverse transcriptase, telomerase. In human cells, insufficient levels of telomerase lead to telomere attrition with cell division in culture and ..
  17. pmc Common variants near TERC are associated with mean telomere length
    Veryan Codd
    Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK
    Nat Genet 42:197-9. 2010
    ..72 x 10(-14)) at a locus that includes TERC, which encodes the telomerase RNA component...
  18. doi Telomeres and aging
    Geraldine Aubert
    Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
    Physiol Rev 88:557-79. 2008
    ..Repair of critically short or "uncapped" telomeres by telomerase or recombination is limited in most somatic cells and apoptosis or cellular senescence is triggered when too ..
  19. pmc Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse
    Matthias Stadtfeld
    Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA
    Cell Stem Cell 2:230-40. 2008
    ..of Thy1 and subsequent upregulation of SSEA-1 occur at early time points, reactivation of endogenous Oct4, Sox2, telomerase, and the silent X chromosome mark late events in the reprogramming process...
  20. pmc Finding the end: recruitment of telomerase to telomeres
    Jayakrishnan Nandakumar
    Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, BioFrontiers Institute, University of Colorado, Boulder, Colorado 80309 0596, USA
    Nat Rev Mol Cell Biol 14:69-82. 2013
    ..and in mammalian germ cells and stem cells, telomere length is maintained by a ribonucleoprotein enzyme known as telomerase. Recent work has provided insights into the mechanisms of telomerase recruitment to telomeres, highlighting the ..
  21. pmc Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer
    Clare Turnbull
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK
    Nat Genet 42:604-7. 2010
    ..Finally, we identified a locus on chromosome 9 (rs755383, OR=1.37, P=1.12x10(-23)), containing the sex determination gene DMRT1, which has been linked to teratoma susceptibility in mice...
  22. pmc Telomerase reverse transcriptase locus polymorphisms and cancer risk: a field synopsis and meta-analysis
    Simone Mocellin
    Department of Oncological and Surgical Sciences, Meta analysis Unit, University of Padova, Padova, Italy
    J Natl Cancer Inst 104:840-54. 2012
    Several recent studies have provided evidence that polymorphisms in the telomerase reverse transcriptase (TERT) gene sequence are associated with cancer development, but a comprehensive synopsis is not available...
  23. pmc Telomerase efficiently elongates highly transcribing telomeres in human cancer cells
    Benjamin O Farnung
    Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich ETHZ, Zurich, Switzerland
    PLoS ONE 7:e35714. 2012
    ..In particular, it has been suggested that TERRA inhibits telomerase activity...
  24. ncbi Protein composition of catalytically active human telomerase from immortal cells
    Scott B Cohen
    Cancer Research Unit, Children s Medical Research Institute, 214 Hawkesbury Road, Westmead NSW 2145, Australia
    Science 315:1850-3. 2007
    b>Telomerase is a ribonucleoprotein enzyme complex that adds 5'-TTAGGG-3' repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for approximately 90% of human cancers...
  25. ncbi Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins
    Ruben D Ramirez
    Hamon Center for Therapeutic Oncology Research and Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Cancer Res 64:9027-34. 2004
    ..culture and serially transfected with retroviral constructs containing cyclin-dependent kinase (Cdk) 4 and human telomerase reverse transcriptase (hTERT), resulting in continuously growing cultures...
  26. pmc The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase
    Sophie Redon
    Swiss Institute for Experimental Cancer Research ISREC, School of Life Sciences, Frontiers in Genetics National Center of Competence in Research, Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
    Nucleic Acids Res 38:5797-806. 2010
    ..as they contain 5'-UUAGGG-3' repeats near their 3'-end which are complementary to the template sequence of telomerase RNA. Here we demonstrate that endogenous TERRA is bound to human telomerase in cell extracts...
  27. ncbi Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends
    Claus M Azzalin
    Swiss Institute for Experimental Cancer Research ISREC, CH 1066 Epalinges, Switzerland
    Science 318:798-801. 2007
    ..Thus, telomeres are actively transcribed into TERRA, and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity...
  28. pmc Reversal of human cellular senescence: roles of the p53 and p16 pathways
    Christian M Beausejour
    Lawrence Berkeley National Laboratory, MS 84 171, 1 Cyclotron Road, Berkeley, CA 94720, USA
    EMBO J 22:4212-22. 2003
    ..Expression of telomerase did not reverse the senescence arrest...
  29. doi Increased telomerase activity and comprehensive lifestyle changes: a pilot study
    Dean Ornish
    Department of Medicine, University of California, San Francisco, CA, USA
    Lancet Oncol 9:1048-57. 2008
    ..Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase ..
  30. doi Telomerase and cancer therapeutics
    Calvin B Harley
    Geron Corporation, 230 Constitution Drive, Menlo Park, California 94025, USA
    Nat Rev Cancer 8:167-79. 2008
    b>Telomerase is an attractive cancer target as it appears to be required in essentially all tumours for immortalization of a subset of cells, including cancer stem cells...
  31. pmc Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians
    Gil Atzmon
    Department of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 107:1710-7. 2010
    ..we studied the inheritance and maintenance of telomere length and variations in two major genes associated with telomerase enzyme activity, hTERT and hTERC...
  32. doi Novel anticancer therapeutics targeting telomerase
    Maria Ruden
    Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL 61107 1822, USA
    Cancer Treat Rev 39:444-56. 2013
    ..each successive cell division in normal human cells whereas, in tumors, they are continuously elongated by human telomerase reverse transcriptase (hTERT)...
  33. pmc Structure of active dimeric human telomerase
    Anselm Sauerwald
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 20:454-60. 2013
    b>Telomerase contains a large RNA subunit, TER, and a protein catalytic subunit, TERT. Whether telomerase functions as a monomer or dimer has been a matter of debate...
  34. pmc TERRA promotes telomere shortening through exonuclease 1-mediated resection of chromosome ends
    Verena Pfeiffer
    Swiss Institute for Experimental Cancer Research ISREC, School of Life Sciences, Frontiers in Genetics National Center of Competence in Research, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    PLoS Genet 8:e1002747. 2012
    ..of EXO1 but not MRE11 fully suppressed the TERRA-mediated short telomere phenotype in presence and absence of telomerase. Thus TERRA transcription facilitates the 5'-3' nuclease activity of Exo1 at chromosome ends, providing a means ..
  35. pmc Collapse of telomere homeostasis in hematopoietic cells caused by heterozygous mutations in telomerase genes
    Geraldine Aubert
    Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
    PLoS Genet 8:e1002696. 2012
    b>Telomerase activity is readily detectable in extracts from human hematopoietic stem and progenitor cells, but appears unable to maintain telomere length with proliferation in vitro and with age in vivo...
  36. ncbi Control of telomere length by the human telomeric protein TRF1
    B van Steensel
    The Rockefeller University, New York 10021, USA
    Nature 385:740-3. 1997
    ..In tumours and immortalized cells, this decline is halted through the activation of telomerase, a reverse transcriptase that extends the telomeric TTAGGG-repeat arrays...
  37. pmc The telomeric Cdc13 protein interacts directly with the telomerase subunit Est1 to bring it to telomeric DNA ends in vitro
    Yun Wu
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Proc Natl Acad Sci U S A 108:20362-9. 2011
    In Saccharomyces cerevisiae, a Cdc13-Est1 interaction is proposed to mediate recruitment of telomerase to DNA ends...
  38. pmc InTERTpreting telomerase structure and function
    Haley D M Wyatt
    London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, EN6 3LD, UK
    Nucleic Acids Res 38:5609-22. 2010
    ..Greider and Jack Szostak for their pioneering studies on chromosome termini (telomeres) and their discovery of telomerase, the enzyme that synthesizes telomeres...
  39. ncbi Telomeres and their control
    M J McEachern
    University of Georgia, Department of Genetics, Athens, Georgia, 30602, USA
    Annu Rev Genet 34:331-358. 2000
    ..This review summarizes the currently known components of the telomere/telomerase functional complex, and focuses on how they act in the control of processes occurring at telomeres...
  40. doi Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress
    Shaheda Ahmed
    Crucible Laboratory, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK
    J Cell Sci 121:1046-53. 2008
    b>Telomerase is a ribonucleoprotein that counteracts telomere shortening and can immortalise human cells. There is also evidence for a telomere-independent survival function of telomerase. However, its mechanism is not understood...
  41. pmc Formation of a unique end-to-end stacked pair of G-quadruplexes in the hTERT core promoter with implications for inhibition of telomerase by G-quadruplex-interactive ligands
    SunMi L Palumbo
    Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, Arizona 85724, USA
    J Am Chem Soc 131:10878-91. 2009
    ..Furthermore, our study implies that inhibition of telomerase activity by some G-quadruplex ligands is not only produced by targeting telomeric G-quadruplexes but also by ..
  42. 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
    ..natural ends from being recognized as sites of DNA damage and also regulates the telomere-replicating enzyme, telomerase. Shelterin includes the heterodimeric POT1-TPP1 protein, which binds the telomeric single-stranded DNA tail...
  43. pmc Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence
    Graeme Hewitt
    Ageing Research Laboratories, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Nat Commun 3:708. 2012
    ..that up to half of the DNA damage foci in stress-induced senescence are located at telomeres irrespective of telomerase activity. Moreover, live-cell imaging experiments reveal that all persistent foci are associated with telomeres...
  44. pmc Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells
    Robert K Montgomery
    Division of Gastroenterology, Children s Hospital Boston, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:179-84. 2011
    ..Here, we identify a subpopulation of slowly cycling ISCs marked by mouse telomerase reverse transcriptase (mTert) expression that can give rise to Lgr5(+) cells...
  45. ncbi Telomeres and telomerase: their mechanisms of action and the effects of altering their functions
    Elizabeth H Blackburn
    Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143 2200, USA
    FEBS Lett 579:859-62. 2005
    The molecular features of telomeres and telomerase are conserved among most eukaryotes. How telomerase and telomeres function and how they interact to promote the chromosome-stabilizing properties of telomeres are discussed here.
  46. pmc Telomeres: protecting chromosomes against genome instability
    Roderick J O'Sullivan
    The Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 11:171-81. 2010
    ..Telomeric proteins and their interacting factors create an environment at chromosome ends that inhibits DNA repair; however, the repair machinery is essential for proper telomere function...
  47. pmc Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
    Francis Rodier
    Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Nat Cell Biol 11:973-9. 2009
    ..Thus, in addition to orchestrating cell-cycle checkpoints and DNA repair, a new and important role of the DDR is to allow damaged cells to communicate their compromised state to the surrounding tissue...
  48. 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
    b>Telomerase contributes to chromosome end replication by synthesizing repeats of telomeric DNA, and the telomeric DNA-binding proteins protection of telomeres (POT1) and TPP1 synergistically increase its repeat addition processivity...
  49. pmc Short telomeres are a risk factor for idiopathic pulmonary fibrosis
    Jonathan K Alder
    Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 105:13051-6. 2008
    ..Short telomeres limit tissue renewal capacity in the lung and germ-line mutations in telomerase components, hTERT and hTR, underlie inheritance in a subset of families with IPF...
  50. ncbi Essential role of mouse telomerase in highly proliferative organs
    H W Lee
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Nature 392:569-74. 1998
    We have investigated the role of the enzyme telomerase in highly proliferative organs in successive generations of mice lacking telomerase RNA...
  51. doi The human CST complex is a terminator of telomerase activity
    Liuh Yow Chen
    Swiss Institute for Experimental Cancer Research ISREC, Ecole Polytechnique Federale de Lausanne, Station 19, 1015 Lausanne, Switzerland
    Nature 488:540-4. 2012
    ..During embryogenesis and in cancer, the telomerase enzyme counteracts telomeric DNA shortening...
  52. doi Telomerase directly regulates NF-κB-dependent transcription
    Arkasubhra Ghosh
    Laboratory of NFκB Signaling, IMCB, Proteos, 138673, Singapore
    Nat Cell Biol 14:1270-81. 2012
    Although elongation of telomeres is thought to be the prime function of reactivated telomerase in cancers, this activity alone does not account for all of the properties that telomerase reactivation attributes to human cancer cells...
  53. pmc TPP1 OB-fold domain controls telomere maintenance by recruiting telomerase to chromosome ends
    Franklin L Zhong
    Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 150:481-94. 2012
    Telomere synthesis in cancer cells and stem cells involves trafficking of telomerase to Cajal bodies, and telomerase is thought to be recruited to telomeres through interactions with telomere-binding proteins...
  54. pmc Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway
    Courtney A Lovejoy
    Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York, United States of America
    PLoS Genet 8:e1002772. 2012
    The Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent pathway for telomere maintenance that is active in a significant subset of human cancers and in vitro immortalized cell lines...
  55. pmc The RNA helicase RHAU (DHX36) unwinds a G4-quadruplex in human telomerase RNA and promotes the formation of the P1 helix template boundary
    E P Booy
    Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada
    Nucleic Acids Res 40:4110-24. 2012
    Human telomerase RNA (hTR) contains several guanine tracts at its 5'-end that can form a G4-quadruplex structure...
  56. pmc Human CST has independent functions during telomere duplex replication and C-strand fill-in
    Feng Wang
    Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati, OH 45267 0521, USA
    Cell Rep 2:1096-103. 2012
    ..Analysis of overhang structure after STN1 depletion revealed normal kinetics for telomerase-mediated extension in S phase but a delay in subsequent overhang shortening...
  57. pmc Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer
    Bruno Bernardes de Jesus
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain
    EMBO Mol Med 4:691-704. 2012
    ..Based on this, we have tested the effects of a telomerase gene therapy in adult (1 year of age) and old (2 years of age) mice...
  58. pmc Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for chromosome end-joining
    Michelle Heacock
    Department of Biochemistry and Biophysics, Texas A and M University, TAMU, College Station, TX 77843 2128, USA
    EMBO J 23:2304-13. 2004
    ..telomere length and examine the fate of dysfunctional telomeres in Arabidopsis lacking the catalytic subunit of telomerase (TERT) and the DNA repair proteins Ku70 and Mre11...
  59. pmc Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells
    Dimitri Conomos
    Cancer Research Unit, Children s Medical Research Institute, Westmead NSW 2145, Australia
    J Cell Biol 199:893-906. 2012
    ..and ALT-associated characteristics were induced after incorporation of the C-type variant repeat by a mutant telomerase. We propose that the presence of variant repeats throughout ALT telomeres results from recombination-mediated ..
  60. ncbi Telomerase mutations in families with idiopathic pulmonary fibrosis
    Mary Y Armanios
    Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    N Engl J Med 356:1317-26. 2007
    ..Germ-line mutations in the genes hTERT and hTR, encoding telomerase reverse transcriptase and telomerase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare ..
  61. pmc Genomic amplification of the human telomerase gene (hTERC) associated with human papillomavirus is related to the progression of uterine cervical dysplasia to invasive cancer
    Hongqian Liu
    Department of Obstetric and Gynecologic, West China Second University Hospital, Sichuan University, Chengdu 610041, China
    Diagn Pathol 7:147. 2012
    ..Amplification of human telomerase gene (hTERC) and over expression of telomerase were found to be associated with cervical tumorigenesis...
  62. pmc Telomerase and telomere-associated proteins: structural insights into mechanism and evolution
    Karen A Lewis
    Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA
    Structure 20:28-39. 2012
    Recent advances in our structural understanding of telomerase and telomere-associated proteins have contributed significantly to elucidating the molecular mechanisms of telomere maintenance...
  63. pmc The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein
    H Qi
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544 1014, USA
    Genes Dev 14:1777-88. 2000
    ..the C(1-3)A strand is degraded to generate a long single strand TG(1-3) tail that can serve as a substrate for telomerase. Cdc13p is a single strand TG(1-3) DNA-binding protein that localizes to telomeres in vivo...
  64. pmc SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay
    Isao Kashima
    Max Planck Institute for Developmental Biology, D 72076 Tubingen, Germany
    Genes Dev 24:2440-50. 2010
    ....
  65. ncbi Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms
    Maria Ester Bernardo
    Oncoematologia Pediatrica, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Universita di Pavia, Pavia, Italy
    Cancer Res 67:9142-9. 2007
    ..MSCs were tested for the expression of telomerase activity, human telomerase reverse transcriptase (hTERT) transcripts, and alternative lengthening of telomere (..
  66. pmc A role for heterochromatin protein 1γ at human telomeres
    Silvia Canudas
    Molecular Pathogenesis Program, Department of Pathology, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
    Genes Dev 25:1807-19. 2011
    ..HP1-binding site in TIN2 is required for sister telomere cohesion and can impact telomere length maintenance by telomerase. Remarkably, the PTVML HP1-binding site is embedded in the recently identified cluster of mutations in TIN2 that ..
  67. doi Telomerase gene mutations are associated with cirrhosis formation
    Daniel Hartmann
    Department on Stem Cell Aging, University of Ulm, Ulm, Germany
    Hepatology 53:1608-17. 2011
    ..In humans, telomerase mutations have been associated with familial diseases leading to bone marrow failure or lung fibrosis...
  68. pmc Telomere shortening in familial and sporadic pulmonary fibrosis
    Jennifer T Cronkhite
    Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390 8591, USA
    Am J Respir Crit Care Med 178:729-37. 2008
    Heterozygous mutations in the coding regions of the telomerase genes, TERT and TERC, have been found in familial and sporadic cases of idiopathic interstitial pneumonia. All affected patients with mutations have short telomeres.
  69. pmc Healthy aging and disease: role for telomere biology?
    Haidong Zhu
    Department of Pediatrics, Georgia Prevention Institute, Medical College of Georgia, Augusta, GA 30912, USA
    Clin Sci (Lond) 120:427-40. 2011
    ..Despite the remarkable progress made during the last two decades, our understanding of the biology of aging remains incomplete. Telomere biology has recently emerged as an important player in the aging and disease process...
  70. doi Spliceosomal cleavage generates the 3' end of telomerase RNA
    Jessica A Box
    Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
    Nature 456:910-4. 2008
    ..The DNA portion of telomeres is synthesized by the enzyme telomerase using part of an RNA subunit as a template for reverse transcription...
  71. doi Spontaneous occurrence of telomeric DNA damage response in the absence of chromosome fusions
    Anthony J Cesare
    Cancer Research Unit, Children s Medical Research Institute, Westmead, New South Wales, Australia
    Nat Struct Mol Biol 16:1244-51. 2009
    ..In telomerase activity-positive (TA(+)) cells, DDR is associated with low TA and short telomeres...
  72. ncbi Break-induced replication and telomerase-independent telomere maintenance require Pol32
    John R Lydeard
    MS029 Rosenstiel Centre, Brandeis University, Waltham, Massachusetts 02454 9110, USA
    Nature 448:820-3. 2007
    ..replication at stalled and broken replication forks and to act at eroding telomeres in cells that lack telomerase in pathways known as 'alternative lengthening of telomeres' (reviewed in refs 2, 6)...
  73. pmc TLC1 RNA nucleo-cytoplasmic trafficking links telomerase biogenesis to its recruitment to telomeres
    Franck Gallardo
    Departement de Biochimie, Universite de Montreal, Montreal, Quebec, Canada
    EMBO J 27:748-57. 2008
    The yeast telomerase holoenzyme, which adds telomeric repeats at the chromosome ends, is composed of the TLC1 RNA and the associated proteins Est1, Est2 and Est3...
  74. pmc Resting leukocyte telomerase activity is elevated in major depression and predicts treatment response
    O M Wolkowitz
    Department of Psychiatry, School of Medicine, University of California, San Francisco UCSF, San Francisco, CA 94143 0984, USA
    Mol Psychiatry 17:164-72. 2012
    ..When telomeres critically shorten, cells become susceptible to senescence and apoptosis. Telomerase, a cellular ribonucleoprotein enzyme, rebuilds the length of telomeres and promotes cellular viability...
  75. pmc Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita
    Mary Armanios
    Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 102:15960-4. 2005
    ..Families with autosomal dominant dyskeratosis congenita display anticipation and have mutations in the telomerase RNA gene...
  76. ncbi 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
    b>Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes...
  77. ncbi Extensive allelic variation and ultrashort telomeres in senescent human cells
    Duncan M Baird
    Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
    Nat Genet 33:203-7. 2003
    ..Superimposed on this are occasional, more substantial changes in length, which may be the consequence of additional mutational mechanisms. Notably, some alleles show almost complete loss of TTAGGG repeats at senescence...
  78. doi Telomerase, mitochondria and oxidative stress
    Gabriele Saretzki
    Crucible Laboratory, Institute for Ageing and Health, International Centre for Life, Bioscience Centre, Central Parkway, Newcastle upon Tyne, United Kingdom
    Exp Gerontol 44:485-92. 2009
    b>Telomerase plays an important role in cellular proliferation capacity and survival under conditions of stress. A large part of this protective function is due to telomere capping and maintenance...
  79. pmc A two-step model for senescence triggered by a single critically short telomere
    Pauline Abdallah
    LBMC, UMR 5239, CNRS ENS Lyon, Universite Lyon 1, Ecole Normale Superieure, 46 allee d Italie, F 69364 Lyon Cedex 07, France
    Nat Cell Biol 11:988-93. 2009
    ..Here, we show that telomerase-deficient cells bearing a single, very short telomere senesce earlier, demonstrating that the length of the ..
  80. pmc N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and SMG-5:SMG-7 during NMD
    Yukiko Okada-Katsuhata
    Department of Molecular Biology, Yokohama City University, School of Medicine, 3 9, Fuku ura, Kanazawa Ku, Yokohama 236 0004, Japan
    Nucleic Acids Res 40:1251-66. 2012
    ....
  81. pmc Regulation of the human catalytic subunit of telomerase (hTERT)
    MICHAEL DANIEL
    Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA
    Gene 498:135-46. 2012
    Over the past decade, there has been much interest in the regulation of telomerase, the enzyme responsible for maintaining the integrity of chromosomal ends, and its crucial role in cellular immortalization, tumorigenesis, and the ..
  82. pmc Role of telomeres and telomerase in cancer
    Jerry W Shay
    UT Southwestern Medical Center, Department of Cell Biology, 5323 Harry Hines Blvd, Dallas, TX 75390 9039, USA
    Semin Cancer Biol 21:349-53. 2011
    There is mounting evidence for the existence of an important relationship between telomeres and telomerase and cellular aging and cancer...
  83. pmc Biogenesis of telomerase ribonucleoproteins
    Emily D Egan
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720 3200, USA
    RNA 18:1747-59. 2012
    b>Telomerase adds simple-sequence repeats to the ends of linear chromosomes to counteract the loss of end sequence inherent in conventional DNA replication...
  84. ncbi TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase
    Huawei Xin
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
    Nature 445:559-62. 2007
    ..Early studies in lower organisms have helped to establish the crucial role of telomerase and telomeric proteins in maintaining telomere length and protecting telomere ends...
  85. ncbi The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability
    M T Hemann
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 107:67-77. 2001
    ..to telomere dysfunction, we crossed mTR-/- G6 mice that have short telomeres with mice heterozygous for telomerase (mTR+/-) that have long telomeres...
  86. doi Frequency of TERT promoter mutations in human cancers
    João Vinagre
    Institute of Molecular Pathology and Immunology of the University of Porto, 4200 465 Porto, Portugal
    Nat Commun 4:2185. 2013
    Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood...
  87. pmc Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells
    Luis F Z Batista
    Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 474:399-402. 2011
    ..In iPSCs from patients with heterozygous mutations in TERT, the telomerase reverse transcriptase, a 50% reduction in telomerase levels blunts the natural telomere elongation that ..
  88. pmc Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer
    Jian Hu
    Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Cell 148:651-63. 2012
    To assess telomerase as a cancer therapeutic target and determine adaptive mechanisms to telomerase inhibition, we modeled telomerase reactivation and subsequent extinction in T cell lymphomas arising in Atm(-/-) mice engineered with an ..
  89. doi Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage
    Judith Haendeler
    Molecular Cardiology, Department of Internal Medicine III, Centre of Biological Chemistry, University of Frankfurt, Germany
    Arterioscler Thromb Vasc Biol 29:929-35. 2009
    The enzyme telomerase and its catalytic subunit the telomerase reverse transcriptase (TERT) are important for maintenance of telomere length in the nucleus. Recent studies provided evidence for a mitochondrial localization of TERT...
  90. pmc Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends
    Anne E Stellwagen
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genes Dev 17:2384-95. 2003
    ..We show that Ku binds TLC1, the RNA component of telomerase. We also describe a novel separation-of-function allele of Ku that is specifically defective in TLC1 binding...
  91. pmc MERISTEM DISORGANIZATION1 encodes TEN1, an essential telomere protein that modulates telomerase processivity in Arabidopsis
    Katherine A Leehy
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas 77843 2128, USA
    Plant Cell 25:1343-54. 2013
    ..However, unlike stn1 or ctc1 mutants, telomerase enzyme activity is elevated in ten1-3 mutants due to an increase in repeat addition processivity...
  92. pmc It all comes together at the ends: telomerase structure, function, and biogenesis
    Joshua D Podlevsky
    Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287 1604, USA
    Mutat Res 730:3-11. 2012
    b>Telomerase is a reverse transcriptase specialized in the addition of telomeric DNA repeats onto the ends of chromosomes...
  93. 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
    ..G-quadruplexes through Hoogsteen base-pairing, serve as only marginal primers for extension by recombinant human telomerase; telomerase stalls after every nucleotide addition...
  94. pmc Telomerase and Tel1p preferentially associate with short telomeres in S. cerevisiae
    Michelle Sabourin
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Mol Cell 27:550-61. 2007
    In diverse organisms, telomerase preferentially elongates short telomeres. We generated a single short telomere in otherwise wild-type (WT) S. cerevisiae cells...
  95. pmc High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions
    Jean Charles Nault
    INSERM, UMR 674, Génomique fonctionnelle des tumeurs solides, IUH, Paris F 75010, France
    Nat Commun 4:2218. 2013
    Somatic mutations activating telomerase reverse-trancriptase promoter were recently identified in several tumour types...
  96. doi Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells
    Rosa M Marion
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Melchor Fernandez Almagro 3, Madrid, Spain
    Cell Stem Cell 4:141-54. 2009
    ..We demonstrate genetically that, during reprogramming, telomere elongation is usually mediated by telomerase and that iPS telomeres acquire the epigenetic marks of ES cells, including a low density of trimethylated ..
  97. pmc TERT promoter mutations in ocular melanoma distinguish between conjunctival and uveal tumours
    K G Griewank
    Department of Dermatology, University Hospital, University Duisburg Essen, Hufelandstrasse 55, Essen, Germany
    Br J Cancer 109:497-501. 2013
    ..Recently, activating mutations in the TERT promoter were identified in cutaneous melanoma. We tested a cohort of ocular melanoma samples for similar mutations...
  98. pmc Human telomerase acts as a hTR-independent reverse transcriptase in mitochondria
    Nilesh K Sharma
    Department of Pharmacology and Physiology, New Jersey Medical School of UMDNJ, 185 South Orange Avenue, Medical Sciences Building, Newark, NJ 07103, USA
    Nucleic Acids Res 40:712-25. 2012
    Human telomerase reverse transcriptase (hTERT) is localized to mitochondria, as well as the nucleus, but details about its biology and function in the organelle remain largely unknown...
  99. pmc Phenotypes in mTERT⁺/⁻ and mTERT⁻/⁻ mice are due to short telomeres, not telomere-independent functions of telomerase reverse transcriptase
    Margaret A Strong
    Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, 603 PCTB, 725 N Wolfe Street, Baltimore, MD 21205, USA
    Mol Cell Biol 31:2369-79. 2011
    b>Telomerase is essential for telomere length maintenance...
  100. pmc Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading-strand replication
    Raghav Chawla
    Institute of Biochemistry, Eidgenössische Technische Hochschule Zürich ETHZ, Zurich, Switzerland
    EMBO J 30:4047-58. 2011
    ..UPF1 physically interacts with the telomeric factor TPP1 and with telomerase. Akin to UPF1 binding to telomeres, this latter interaction is mediated by ATR...
  101. ncbi The yeast Pif1p helicase removes telomerase from telomeric DNA
    Jean Baptiste Boulé
    Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
    Nature 438:57-61. 2005
    ..Genetic studies have established that the baker's yeast Pif1p DNA helicase is a negative regulator of telomerase, the specialized reverse transcriptase that maintains telomeric DNA, but the biochemical basis for this ..

Research Grants75

  1. OLIGOCLONAL T CELL EXPANSION AND RHEUMATOID ARTHRITIS
    Cornelia M Weyand; Fiscal Year: 2012
    ..In search of the underlying molecular defect, we have found that RA patients fail to induce sufficient telomerase during the priming response of na[unreadable]ve CD4 T cells...
  2. A novel telomerase expressing lung fibroblast phenotype
    Sem H Phan; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The broad long term objective is to elucidate the role of telomerase induction in pathogenesis of chronic fibrotic lung diseases, such as interstitial lung diseases, chronic obstructive pulmonary ..
  3. PRE- AND POSTGRADUATE TRAINING IN MOLECULAR HEMATOLOGY
    J Evan Sadler; Fiscal Year: 2013
    ..lysosomal storage diseases;phosphoinositide metabolism and cell signaling pathways;mechanisms of hematopoiesis;telomerase and ribosomal protein defects in bone marrow failure syndromes;molecular basis for protein trafficking in ..
  4. Protein composition and interactions of telemeric chromatin
    Michael P Killoran; Fiscal Year: 2010
    ..In -90% of human cancers, the increased expression of telomerase further facilitates tumorigenesis by providing a selective advantage over surrounding cells that are normally ..
  5. Herpesvirus-induced telomerase dysregulation and tumor formation
    Keith William Jarosinski; Fiscal Year: 2011
    ..Tumorigenesis requires the continued survival of once transformed cells, which is critically dependent on telomerase activity to avoid cellular senescence and apoptosis...
  6. Molecular Studies of Bone Marrow Failure
    Monica Bessler; Fiscal Year: 2013
    ..period we investigated the frequency, heritability, penetrance, and expressivity of mutations in TERC and in the telomerase catalytic subunit TERT in patients diagnosed with BMF and their families...
  7. Enterovirus RNA Translation and Replication
    David J Barton; Fiscal Year: 2013
    ..assembles polysomes uncoupled from host cell mRNA turnover machinery, 2) we discovered an evolutionarily ancient telomerase-like mechanism of RNA replication that maintains the integrity of the poly(A) tail at the 3'end of viral ..
  8. Telomere and its bio-regulators as predictors for clinical diabetes in women
    Simin Liu; Fiscal Year: 2010
    ..examine whether single nucleotide polymorphisms (SNPs) on the genes coding for telomere-binding proteins and telomerase maintenance may explain the individual variability in telomere length and whether these SNPs would be ..
  9. Mouse Models of Non-Syndromic Cardiac Progeria
    Ali J Marian; Fiscal Year: 2012
    ..senescence-associated 2-galactosidase (S-A 2-Gal), p16INK4a (Cdkn2a), P19, p21WAF1/CIP1, telomere attrition and telomerase activity...
  10. Studying a Human Stem Cell Disease Using iPS Technology
    Steven E Artandi; Fiscal Year: 2010
    ..DC is caused by mutations in telomerase genes or genes encoding telomere binding proteins...
  11. The role fo the TPP1 peotein in telomerase function and cancer cell survival
    Jayakrishnan Nandakumar; Fiscal Year: 2013
    Summary: Mammalian telomerase is a specialized reverse transcriptase that extends the 3'ends of chromosomes with telomeric DNA...
  12. Human Papillomavirus Association with Subsets of Colorectal Cancer
    Polly A Newcomb; Fiscal Year: 2010
    ..These interfere with tumor suppressor proteins p53 and pRb and induce telomerase, thereby immortalizing cells. Thus, HPV-related tumors infrequently contain p53 mutations...
  13. Defining the telomerase holoenzyme in progenitor cells with aging
    Steven E Artandi; Fiscal Year: 2013
    ..provided by applicant): Telomeres, the nucleoprotein structures that cap chromosome ends, are maintained by telomerase, a multi-subunit enzyme complex...
  14. Separation-of-function Mutants to Study the Biological Significance of Telomerase
    Jayakrishnan Nandakumar; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Mammalian telomerase is a specialized reverse transcriptase that extends the 3'ends of chromosomes with telomeric DNA...
  15. Role of dyskerin in oral epithelial homeostasis
    Faizan Alawi; Fiscal Year: 2013
    ..It is in this capacity that dyskerin contributes to telomerase activity and precursor rRNA processing...
  16. DNA-PKcs Phosphorylation on Hematopoietic Stem Cells Genome Maintenance
    Benjamin Ping Chi Chen; Fiscal Year: 2013
    ..human dyskeratosis congenita (DC) syndrome and in mice double knockout of protection of telomeres 1b (POT1b) and telomerase RNA (mTR) genes. In addition, DC patients are also prone to cancer development...
  17. Accelerated Biologic Aging and Risk for Sepsis and Organ Failure Following Trauma
    ELIZABETH GROOMS NESMITH; Fiscal Year: 2012
    ..AAs and persons of low SES report chronic stress, which has been linked to accelerated biologic aging via telomerase activity...
  18. IGF-1, Gender, Heart Failure and Longevity: A Paradigm Shift
    Piero Anversa; Fiscal Year: 2010
    ..The fundamental premise of this research is that estrogen enhances telomerase function and IGF-1 signaling in CPCs promoting CPC division and lineage commitment...
  19. 2011 Cold Spring Harbor Conference on Telomeres and Telomerase
    David J Stewart; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Cold Spring Harbor Laboratory Conference on Telomeres and Telomerase May 3-7, 2011. Telomeres are specialized protein-DNA complexes that protect the ends of eukaryotic chromosomes...
  20. Regulation and Function of hTERT in Human Cells
    William C Hahn; Fiscal Year: 2013
    ..Indeed, studies in both human and animal models indicate that telomeres and telomerase, the reverse transcriptase that maintains telomere structure, serve dual roles in oncogenesis, acting both to ..
  21. Determining the Roles of ATRX and DAXX Abnormalities in Cancer Telomere Biology
    ALAN KEITH MEEKER; Fiscal Year: 2013
    ..In contrast, many cancers preserve their telomeres by co-opting the telomere-specific reverse transcriptase telomerase, which has been intensively studied as a potential target for anti-cancer therapy...
  22. Group II Intron Mobility and Gene Targeting
    Alan M Lambowitz; Fiscal Year: 2012
    ..a reverse transcriptase and are thought to be evolutionary ancestors of spliceosomal introns, retroelements, and telomerase in higher organisms...
  23. Effects of exercise and life stress on telomere maintenance and CVD risk
    Eli Puterman; Fiscal Year: 2013
    ..Human and mouse studies support the critical role that the telomere/telomerase maintenance system plays in cardiovascular disease and mortality...
  24. Effects of exercise and life stress on telomere maintenance and CVD risk
    Eli Puterman; Fiscal Year: 2012
    ..Human and mouse studies support the critical role that the telomere/telomerase maintenance system plays in cardiovascular disease and mortality...
  25. Telomere extension using nucleoside-modified mRNA and exosomes as a novel therape
    Helen M Blau; Fiscal Year: 2013
    ..The enzyme telomerase extends telomeres, and the limiting component of telomerase in most cells is telomerase reverse transcriptase (..
  26. Role of Angiogenic CXC Chemokines in Intramembranous Bone Repair
    Dean T Yamaguchi; Fiscal Year: 2013
    ..Experiments will be done in human MSCs (hMSCs) that have been transduced to express human telomerase reverse transcriptase (TERT) to enhance their longevity in vitro...
  27. Telomeres and lung cancer incidence and survival
    Jennifer Anne Doherty; Fiscal Year: 2013
    ..Recently, several large-scale genome-wide association studies have reported that SNPs in the telomerase reverse transcriptase (TERT) gene are strongly associated with lung cancer risk...
  28. 2nd ASM Conference on Manipulation of Nuclear Processes by DNA Viruses
    Laimonis A Laimins; Fiscal Year: 2011
    ..viruses and the stress response 3). viral remodeling of the nucleus and telomerase activation 4). viruses and cancer 5). transcriptional control and miRNA regulation 6)...
  29. Tumor-cell-specific targets for combined hyperthermia and radiation effects
    Tej K Pandita; Fiscal Year: 2013
    ..expressed (present) in tumor cells? One such factor, expressed in most tumors and silent in somatic cells, is telomerase. Moreover, differences in telomerase activity and cell kinetics between normal and tumor tissues suggest that ..
  30. Structure and dynamics of the Tetrahymena telomerase ribonucleoprotein
    Michael D Stone; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The telomerase ribonucleoprotein (RNP) is required for maintaining telomeres, the specialized nucleoprotein structures that protect eukaryotic chromosome ends from aberrant processing and deleterious ..
  31. RNA Dynamics of Transient Macromolecular Complexes in Cancer Cells
    Jack D Keene; Fiscal Year: 2013
    ..state in primary epithelial cells using methods pioneered in the laboratory of Robert Weinberg with RAS, telomerase and four other transforming proteins quantify dynamic changes in RNAs associated with HuR (early response gene ..
  32. Telomere Shortening and Stem Cell Maintenance
    Mary Y Armanios; Fiscal Year: 2010
    ..The molecular determinants of stem cells in health and cancer are not known. Telomerase is a specialized DNA polymerase responsible for telomere addition by using an intrinsic RNA template...
  33. DNA REPLICATION AND CHROMOSOME STRUCTURE IN YEAST
    Virginia A Zakian; Fiscal Year: 2013
    ..cerevisiae Pif1. The first aim will determine how the S. cerevisiae Pif1 inhibits telomerase- mediated telomere extension by asking if Pif1 inhibits the frequency and/or extent of telomere lengthening and ..
  34. Redefining Human Myocardial Biology
    Annarosa Leri; Fiscal Year: 2013
    ..of DNA damage and telomere dysfunction induced foci (TIFs) to determine the integrity of the telomere-telomerase axis;and e) The mechanical, electrical and calcium transient characteristics of myocytes to evaluate the effects ..
  35. Comparative Analysis of DNA Break Repair in Short- and Long-Lived Rodent Species
    Vera Gorbunova; Fiscal Year: 2012
    ..a collection of primary cells and tissues from 17 rodent species, and performed preliminary analysis of telomerase activity, cell growth characteristics, and genome stability in these cells...
  36. Elucidating the role of TIN2L at the telomere and in dyskeratosis congenita
    Nya D Nelson; Fiscal Year: 2013
    ..this, six of the seven genes mutated in DC encode components or factors required for the assembly or activity of telomerase, the enzyme that replenishes terminal telomeric repeats following DNA replication...
  37. Chronic and Acute Psychosocial Stress and Impaired Cell Aging
    Elissa S Epel; Fiscal Year: 2013
    ..We found support for this hypothesis using the telomere length/telomerase maintenance system as an index of cell aging in vivo...
  38. Stress, Cellular Aging and Susceptibility to Infectious Disease
    Sheldon A Cohen; Fiscal Year: 2010
    ..Moreover, psychological stress has also been associated with greater oxidative stress and less telomerase activity...
  39. Studying a bone marrow failure disease using patient-specific iPS cells
    LUIS ZIRNBERGER BATISTA; Fiscal Year: 2013
    ..All mutations discovered in DC so far were in genes related to telomere homeostasis, either in telomerase, or directly binding to telomeres...
  40. UNIVERSITY OF TEXAS SPORE IN LUNG CANCER
    John D Minna; Fiscal Year: 2013
    ..new targets for chemoprevention and therapy of lung cancer;and developing lung cancer therapies directed against telomerase. To achieve these goals, our SPORE has assembled clinicians and basic scientists including medical oncologists, ..
  41. Stress, Mood, Omega-3 Fatty Acids, &Telomeric Aging: Randomized Controlled Trial
    Janice K Kiecolt-Glaser; Fiscal Year: 2012
    ..provided by applicant): Telomeres are important for chromosomal stability and replication, and the enzyme telomerase is important for telomere formation, maintenance, and restoration...
  42. DNA/RNA G-Quadruplexes: Structures, Transitions and Recognition
    Dinshaw J Patel; Fiscal Year: 2013
    ..Ligand-induced stabilization of telomeric G-quadruplex scaffolds in humans, resulting in the inhibition of telomerase activity, constitutes a promising strategy for anti-cancer drug development...
  43. Colorectal Cancer Prevention Through Thyroid Hormone Targets
    ADAM ROBERT BROWN; Fiscal Year: 2013
    ..will be extracted from adenomas and uninvolved mucosa and expression levels of KLF9, TR[unreadable]1, FASN, and telomerase reverse transcriptase (TERT) will be evaluated by Western blot and qPCR...
  44. Functional Interactions of Telomere Protein with Human Telomerase
    THOMAS ROBERT CECH; Fiscal Year: 2013
    ..stability, yet telomeric DNA must also be accessible to interact with the chromosome end-replicating enzyme, telomerase. Recent work indicates that the human telomeric protein TPP1, which forms a heterodimer with POT1 and binds the ..
  45. A Study of Telomeres in an Arsenic-Exposed Bangladesh Cohort
    BRANDON LEE PIERCE; Fiscal Year: 2013
    ..are central to the regulation of genome stability, and arsenic has detrimental effects on telomeres and telomerase, the primary telomere maintenance enzyme, in a wide variety of experimental settings...
  46. Immunoregulation and immunotherapy of breast cancer
    Robert H Vonderheide; Fiscal Year: 2012
    ..This proposal addresses these obstacles in breast cancer by combining a novel vaccine against the human telomerase reverse transcriptase (hTERT) and survivin in combination with anti-CD25 antibody daclizumab in patients with ..
  47. Telomere length, telomere maintenance genes and cancer risk
    LISA ALLYN BOARDMAN; Fiscal Year: 2012
    ..Third, MSS CRC exhibits the telomerase dependent pathway that the majority of telomere maintenance genes follow...
  48. The Role of the Human Holliday Junction Resolvase Component SLX4 in DNA Recombina
    MOHAMED FIRAZ MOHIDEEN; Fiscal Year: 2013
    ..SLX4 has been observed at telomeres in telomerase- negative (ALT) cells and a recent study highlights the importance of MUS81, a subunit of the SLX4 complex, in ..
  49. STRUCTURE AND BEHAVIOR OF YEAST TELOMERES
    Virginia A Zakian; Fiscal Year: 2013
    ..of linear molecules, in most eukaryotes, telomeric DNA is maintained by a specialized reverse transcriptase, telomerase. The long term goal of this grant is to elucidate mechanisms that enable telomeres to fulfill their varied ..
  50. Investigating the Role of the Est1p in Telomerase Biogenesis and Regulation
    Charlene Hawkins; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The ribonucleoprotein complex, telomerase, functions to counteract the gradual telomere shortening that dividing cells experience when the conventional DNA replication machinery fails to fully ..
  51. Cell Cycle Regulation of Yeast Telomerase Assembly and Function
    KATHERINE LOUISE FRIEDMAN; Fiscal Year: 2012
    Project Summary The ribonucleoprotein complex, telomerase, counteracts loss of terminal sequences during DNA replication...
  52. Telomerace Recruitment to Telomeres Via Core Telomore Binding Proteins
    Eladio Abreu; Fiscal Year: 2010
    ..This process limits the proliferative capacity of most cell types. Telomerase is the enzyme responsible for synthesizing the repetitive DNA that comprises the telomere...
  53. Control of Telomere Heterochromatin by TERRA
    Paul M Lieberman; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Telomeres and telomerase play a critical role in cellular aging and human carcinogenesis...
  54. Adoptive transfer of gene-modified autologous T-cells post-ASCT for myeloma
    Aaron P Rapoport; Fiscal Year: 2013
    ..proportion of patients against a putative tumor antigen vaccine composed of peptides derived from human telomerase (hTERT) and survivin...
  55. Reactive Oxygen Species and Telomeres in Cardiovascular Disease
    CARRIE ANN JESSICA OLIVIA GORDON; Fiscal Year: 2013
    ..Recently published reports have identified ROS as a regulator of TERT, the catalytic subunit of telomerase, which uses its enzymatic activity to maintain telomere length...
  56. Molecular Determinants that Govern Ku's Association with Telomeres
    SANDRA MELANIE LOUISE INDIVIGLIO; Fiscal Year: 2012
    ..certain stem cells, ensure sufficient telomere length is by having the telomere-specific reverse transcriptase telomerase active...
  57. Oncogenes and oncogenic microRNAs in chicken tumors
    Karen L Beemon; Fiscal Year: 2012
    ..In humans, but not mice, activation of telomerase reverse transcriptase (TERT) is also observed in ~90% of tumors...
  58. Analysis of Hif1alpha-mediated Regulation of Telomerase &Telomeres in Stem Cells
    Richard C Allsopp; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The long term goal of this research is to understand the mechanisms of telomerase regulation in stem cells, which we know very little about at present, to facilitate the development of therapies to ..
  59. Functions of the BLM Helicase in Telomere Maintenance
    JOANNA LOUISE GRODEN; Fiscal Year: 2012
    ..or ALT (alternative lengthening of telomeres), processes that maintain/elongate telomeres in the absence of telomerase. BLM preferentially associates with the telomere- specific binding proteins TRF1 and TRF2 in cells using ALT;its ..
  60. Biogenesis and Regulation of Human Telomerase
    Kathleen Collins; Fiscal Year: 2013
    b>Telomerase elongates chromosome ends by addition of tandem telomeric repeats. This new DNA synthesis is required to balance the loss of DNA that is inherent in the incomplete replication of chromosome ends by conventional DNA polymerases...
  61. The Pathogenesis of Dyskeratosis Congenita
    Philip J Mason; Fiscal Year: 2013
    ..All forms of DC are known to have mutations in components of telomerase or shelterin, the telomere associated complex...
  62. Epigenetic determinants of Epstein-Barr virus and cellular DNA in oral diseases
    SHANNON CELESTE KENNEY; Fiscal Year: 2013
    ..We recently identified a telomerase immortalized normal oral keratinocyte (NOK) line that can be stably EBV infected, demonstrated that EBV+ NOKs ..
  63. Amplification of Cardiosphere-Derived Cell Therapy
    BRIAN RAYMOND WEIL; Fiscal Year: 2013
    ..of potential mechanisms underlying the hypothesized differences between these cell populations, Y-CDC and A-CDC telomerase activity and telomere length will be assessed in Aim 3...
  64. STRUCTURAL AND FUNCTIONAL ANALYSIS OF TELOMERASE RNAS
    Daniel Romero; Fiscal Year: 1999
    ..Telomeric DNA is maintained by a ribonucleoprotein enzyme (telomerase) whose RNA moiety serves as a template, dictating the species-specific telomeric DNA repeat synthesized...
  65. DNA REPLICATION AND CHROMOSOME STRUCTURE IN YEAST
    Virginia Zakian; Fiscal Year: 2009
    ..Yeast telomeric DNA is normally synthesized by the reverse transcriptase telomerase, although recombination can maintain yeast telomeric DNA in cells lacking telomerase...
  66. Chronic and Acute Psychosocial Stress and Impaired Cell Aging
    Elissa Epel; Fiscal Year: 2009
    ..We found support for this hypothesis using the telomere length/telomerase maintenance system as an index of cell aging in vivo...
  67. Investigating Telomerase Mechanism by Exploring the RNA
    David C Zappulla; Fiscal Year: 2010
    ..My research concerns telomerase, which replicates the ends of eukaryotic chromosomes and is composed of an RNA as well as several protein ..
  68. OVERCOMING CELLULAR SENESCENCE IN HUMAN EPITHELIAL CELLS
    Aloysius Klingelhutz; Fiscal Year: 2004
    ..The hypothesis to be tested is that both the abrogation of the retinoblastoma pathway and activation of telomerase is necessary for epithelial cells to overcome senescence...
  69. TELOMERE AND TELOMERASE INTERACTIVE AGENTS
    Daniel Von Hoff; Fiscal Year: 1999
    The overall goal of this project is to develop telomere and telomerase interactive agents that improve the survival and quality of life of patients with cancer...
  70. DNA Methylation in Early Detection of Prostate Cancer
    Steven Smith; Fiscal Year: 2002
    ..Recent reports have identified two candidate markers for the early detection of prostate cancer: telomerase and methylation status...
  71. Sphingosine-1-phosphate-activated telomerase in stroke
    Christian Waeber; Fiscal Year: 2006
    ..In brain EC, sphingosine-1 -phosphate (S1P) activates Akt and telomerase, suppresses apoptosis and induces proliferation...
  72. In Vitro Reconstitution and Biochemical Characterization of Yeast Telomerase
    KAREN ADELL LEWIS; Fiscal Year: 2012
    ..senescence, which is avoided in rapidly proliferating cells by the activation of the reverse transcriptase telomerase. Telomerase is a ribonucleoprotein that adds tandem repeats to the ends of telomeres to maintain length, and is ..
  73. TELOMERASE RNP STRUCTURE/FUNCTION
    DOROTHY SHIPPEN; Fiscal Year: 2001
    ..The primary mechanism for synthesizing teleomeres is telomerase, an unusual ribonucleoprotein (RNP) with reverse transcriptase activity...
  74. CSHL Conference on Telomeres and telomerase
    TERRI GRODZICKER; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Cold Spring Harbor Laboratory Conference on Telomeres and Telomerase May 2-6, 2007 Telomeres are specialized protein-DNA complexes that protect the ends of eukaryotic chromosomes...
  75. CSHL 2009 Conference on Telomeres and Telomerase
    David Stewart; Fiscal Year: 2009
    Cold Spring Harbor Laboratory Conference on Telomeres and Telomerase April 28-May 2, 2009 Telomeres are specialized protein-DNA complexes that protect the ends of eukaryotic chromosomes...