telomere

Summary

Summary: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.

Top Publications

  1. pmc TERRA: telomeric repeat-containing RNA
    Brian Luke
    EPFL Ecole Polytechnique Fédérale de Lausanne, ISREC Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland
    EMBO J 28:2503-10. 2009
  2. pmc Telomere measurement by quantitative PCR
    Richard M Cawthon
    Department of Human Genetics, University of Utah, 15 N 2030 E, Room 2100, Salt Lake City, UT 84112, USA
    Nucleic Acids Res 30:e47. 2002
  3. pmc Removal of shelterin reveals the telomere end-protection problem
    Agnel Sfeir
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Science 336:593-7. 2012
  4. ncbi How shelterin protects mammalian telomeres
    Wilhelm Palm
    Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA
    Annu Rev Genet 42:301-34. 2008
  5. ncbi Shelterin: the protein complex that shapes and safeguards human telomeres
    Titia de Lange
    The Rockefeller University, New York, New York 10021, USA
    Genes Dev 19:2100-10. 2005
  6. 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
  7. ncbi A DNA damage checkpoint response in telomere-initiated senescence
    Fabrizio d'Adda di Fagagna
    1 The Wellcome Trust Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QR, UK 2 Present address IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy
    Nature 426:194-8. 2003
  8. pmc Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication
    Agnel Sfeir
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Cell 138:90-103. 2009
  9. 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
  10. ncbi Oxidative stress shortens telomeres
    Thomas von Zglinicki
    Dept Gerontology, University of Newcastle, Wolfson Research Centre, General Hospital, Newcastle upon Tyne, UK
    Trends Biochem Sci 27:339-44. 2002

Detail Information

Publications393 found, 100 shown here

  1. pmc TERRA: telomeric repeat-containing RNA
    Brian Luke
    EPFL Ecole Polytechnique Fédérale de Lausanne, ISREC Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland
    EMBO J 28:2503-10. 2009
    ..at most or all chromosome ends and it is regulated by RNA surveillance factors and in response to changes in telomere length...
  2. pmc Telomere measurement by quantitative PCR
    Richard M Cawthon
    Department of Human Genetics, University of Utah, 15 N 2030 E, Room 2100, Salt Lake City, UT 84112, USA
    Nucleic Acids Res 30:e47. 2002
    ..This assay will facilitate investigations of the biology of telomeres and the roles they play in the molecular pathophysiology of diseases and aging...
  3. pmc Removal of shelterin reveals the telomere end-protection problem
    Agnel Sfeir
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Science 336:593-7. 2012
    The telomere end-protection problem is defined by the aggregate of DNA damage signaling and repair pathways that require repression at telomeres...
  4. ncbi How shelterin protects mammalian telomeres
    Wilhelm Palm
    Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA
    Annu Rev Genet 42:301-34. 2008
    ..shelterin, that functions to protect chromosome ends from all aspects of the DNA damage response and regulates telomere maintenance by telomerase...
  5. ncbi Shelterin: the protein complex that shapes and safeguards human telomeres
    Titia de Lange
    The Rockefeller University, New York, New York 10021, USA
    Genes Dev 19:2100-10. 2005
    Added by telomerase, arrays of TTAGGG repeats specify the ends of human chromosomes. A complex formed by six telomere-specific proteins associates with this sequence and protects chromosome ends...
  6. 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
    ..at telomeres in vivo, negatively regulate TERRA association with chromatin, and protect chromosome ends from telomere loss...
  7. ncbi A DNA damage checkpoint response in telomere-initiated senescence
    Fabrizio d'Adda di Fagagna
    1 The Wellcome Trust Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QR, UK 2 Present address IFOM FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy
    Nature 426:194-8. 2003
    ..Thus, we propose that telomere-initiated senescence reflects a DNA damage checkpoint response that is activated with a direct contribution from ..
  8. pmc Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication
    Agnel Sfeir
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Cell 138:90-103. 2009
    ..Two helicases implicated in the removal of G4 DNA structures, BLM and RTEL1, were required to repress the fragile-telomere phenotype...
  9. 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
    ..the protective DNA-protein complexes at eukaryotic chromosomal ends, and several molecular mechanisms involved in telomere functions...
  10. ncbi Oxidative stress shortens telomeres
    Thomas von Zglinicki
    Dept Gerontology, University of Newcastle, Wolfson Research Centre, General Hospital, Newcastle upon Tyne, UK
    Trends Biochem Sci 27:339-44. 2002
    ..damage is repaired less well in telomeric DNA than elsewhere in the chromosome, and oxidative stress accelerates telomere loss, whereas antioxidants decelerate it...
  11. pmc Distinct factors control histone variant H3.3 localization at specific genomic regions
    Aaron D Goldberg
    Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Cell 140:678-91. 2010
    ..3 at telomeres and for the repression of telomeric RNA. Our data demonstrate that multiple and distinct factors are responsible for H3.3 localization at specific genomic locations in mammalian cells...
  12. 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
    ..It has been proposed that telomere shortening is the molecular clock that triggers senescence...
  13. pmc Accelerated telomere shortening in response to life stress
    Elissa S Epel
    Department of Psychiatry, University of California, 3333 California Street, Suite 465, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 101:17312-5. 2004
    ..of stress--is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from ..
  14. pmc How telomeres solve the end-protection problem
    Titia de Lange
    Laboratory of Cell Biology and Genetics, Rockefeller University, New York, NY 10021, USA
    Science 326:948-52. 2009
    ..Telomeres appear to be tailored to these variations, explaining their variable structure and composition...
  15. pmc The telomere syndromes
    Mary Armanios
    Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Nat Rev Genet 13:693-704. 2012
    There has been mounting evidence of a causal role for telomere dysfunction in a number of degenerative disorders. Their manifestations encompass common disease states such as idiopathic pulmonary fibrosis and bone marrow failure...
  16. pmc CTC1 deletion results in defective telomere replication, leading to catastrophic telomere loss and stem cell exhaustion
    Peili Gu
    Department of Laboratory Medicine and Pathology, Yale University School of Medicine, New Haven, CT 06520 8035, USA
    EMBO J 31:2309-21. 2012
    The proper maintenance of telomeres is essential for genome stability. Mammalian telomere maintenance is governed by a number of telomere binding proteins, including the newly identified CTC1-STN1-TEN1 (CST) complex...
  17. 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...
  18. pmc Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
    Stig E Bojesen
    Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
    Nat Genet 45:371-84, 384e1-2. 2013
    TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers...
  19. ncbi DNA damage foci at dysfunctional telomeres
    Hiroyuki Takai
    Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA
    Curr Biol 13:1549-56. 2003
    We report cytologic and genetic data indicating that telomere dysfunction induces a DNA damage response in mammalian cells...
  20. pmc Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres
    Peter W Lewis
    Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, 1230 York Ave, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:14075-80. 2010
    ..These data demonstrate that Daxx functions as an H3.3-specific chaperone and facilitates the deposition of H3.3 at heterochromatin loci in the context of the ATRX-Daxx complex...
  21. ncbi Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
    Judith Campisi
    Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Cell 120:513-22. 2005
    ..Thus, the senescence response may be antagonistically pleiotropic, promoting early-life survival by curtailing the development of cancer but eventually limiting longevity as dysfunctional senescent cells accumulate...
  22. ncbi G-quadruplex structures: in vivo evidence and function
    Hans J Lipps
    Institute of Cell Biology, University Witten Herdecke, Stockumer Str 10, 58448 Witten, Germany
    Trends Cell Biol 19:414-22. 2009
    ..potential, suggesting that G-quadruplexes could provide a nucleic-acid-based mechanism for regulating telomere maintenance, as well as transcription, replication and translation...
  23. ncbi Crystal structure of parallel quadruplexes from human telomeric DNA
    Gary N Parkinson
    The Cancer Research UK Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Nature 417:876-80. 2002
    ..Disruption of telomere maintenance leads to eventual cell death, which can be exploited for therapeutic intervention in cancer...
  24. ncbi Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a)
    Utz Herbig
    Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA
    Mol Cell 14:501-13. 2004
    Cellular senescence can be triggered by telomere shortening as well as a variety of stresses and signaling imbalances...
  25. pmc Telomeric 3' overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CST
    Peng Wu
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Cell 150:39-52. 2012
    ..telomeres, but its synthesis must be regulated to avoid excessive resection of the 5' end, which could cause telomere shortening. How this balance is achieved in mammals has not been resolved...
  26. ncbi Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1
    Eros Lazzerini Denchi
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 448:1068-71. 2007
    ..by the phosphorylation of the ATR target CHK1 in senescent cells and the response of ATM-deficient cells to telomere dysfunction...
  27. 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
    ..b>Telomere shortening has been shown to contribute to a persistent DNA damage response (DDR) during replicative senescence, ..
  28. ncbi Telomeres and human disease: ageing, cancer and beyond
    Maria A Blasco
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, 28029 Madrid, Spain
    Nat Rev Genet 6:611-22. 2005
    b>Telomere length and telomerase activity are important factors in the pathobiology of human disease...
  29. 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
    b>Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues...
  30. pmc Identification of seven loci affecting mean telomere length and their association with disease
    Veryan Codd
    Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
    Nat Genet 45:422-7, 427e1-2. 2013
    Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases...
  31. 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
    ..complex that protects the natural ends from being recognized as sites of DNA damage and also regulates the telomere-replicating enzyme, telomerase...
  32. pmc TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA
    Rachel Litman Flynn
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Nature 471:532-6. 2011
    Maintenance of telomeres requires both DNA replication and telomere 'capping' by shelterin. These two processes use two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomeres 1 (POT1)...
  33. pmc Telomere length measurement by a novel monochrome multiplex quantitative PCR method
    Richard M Cawthon
    Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA
    Nucleic Acids Res 37:e21. 2009
    The current quantitative polymerase chain reaction (QPCR) assay of telomere length measures telomere (T) signals in experimental DNA samples in one set of reaction wells, and single copy gene (S) signals in separate wells, in comparison ..
  34. 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
    ..b>Telomere loss and uncapping provokes progressive tissue atrophy, stem cell depletion, organ system failure and impaired ..
  35. ncbi Obesity, cigarette smoking, and telomere length in women
    A M Valdes
    Twin Research and Genetic Epidemiology Unit, St Thomas Hospital, London, UK
    Lancet 366:662-4. 2005
    ..Both are states of heightened oxidative stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances white blood cell turnover...
  36. pmc Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation
    Marzia Fumagalli
    IFOM Foundation FIRC Institute of Molecular Oncology Foundation, Milan 20139, Italy
    Nat Cell Biol 14:355-65. 2012
    ..We propose that linear genomes are not uniformly reparable and that telomeric DNA tracts, if damaged, are irreparable and trigger persistent DDR and cellular senescence...
  37. ncbi Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1α
    Nausica Arnoult
    Genetic and Epigenetic Alterations of Genomes, de Duve Institute, Faculty of Pharmacy and Biomedical Sciences, Catholic University of Louvain, Brussels, Belgium
    Nat Struct Mol Biol 19:948-56. 2012
    Gene silencing by the repressive telomeric chromatin environment, referred to as telomere position effect (TPE), has been well characterized in yeast and depends on telomere length...
  38. 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
    b>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...
  39. pmc Purification of proteins associated with specific genomic Loci
    Jérôme Déjardin
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Cell 136:175-86. 2009
    ..We identified and validated several proteins, including orphan nuclear receptors, that specifically bind to ALT telomeres, establishing PICh as a useful tool for characterizing chromatin composition...
  40. ncbi Structure of the human telomere in K+ solution: an intramolecular (3 + 1) G-quadruplex scaffold
    Kim Ngoc Luu
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Am Chem Soc 128:9963-70. 2006
    ..The topological characteristics of this (3 + 1) G-quadruplex scaffold should provide a unique platform for structure-based anticancer drug design targeted to human telomeric DNA...
  41. ncbi Alternative lengthening of telomeres: models, mechanisms and implications
    Anthony J Cesare
    Cancer Research Unit, Childrens Medical Research Institute, Sydney, New South Wales, Australia
    Nat Rev Genet 11:319-30. 2010
    Unlimited cellular proliferation depends on counteracting the telomere attrition that accompanies DNA replication...
  42. 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
    Loss of telomere function can induce cell cycle arrest and apoptosis...
  43. pmc TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres
    Zhong Deng
    The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
    Mol Cell 35:403-13. 2009
    b>Telomere-repeat-encoding RNA (referred to as TERRA) has been identified as a potential component of yeast and mammalian telomeres...
  44. pmc CpG-island promoters drive transcription of human telomeres
    Solomon G Nergadze
    Dipartimento di Genetica e Microbiologia Adriano Buzzati Traverso, Universita di Pavia, 2700 Pavia, Italy
    RNA 15:2186-94. 2009
    ..The existence of subtelomeric promoters, driving TERRA transcription from independent chromosome ends, supports the idea that TERRA exerts fundamental functions in the context of telomere biology.
  45. ncbi Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer
    Stephen Neidle
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, London, UK
    FEBS J 277:1118-25. 2010
    ..In cancer cells, these are associated with the telomere-maintenance enzyme telomerase together with the end-binding protein hPOT1...
  46. pmc Altered telomeres in tumors with ATRX and DAXX mutations
    Christopher M Heaphy
    Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
    Science 333:425. 2011
    ..mutations of these genes are common in human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status of these tumors...
  47. ncbi 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
    ..b>Telomere protection requires a minimal length of TTAGGG repeats to allow the binding of shelterin, which prevents the ..
  48. ncbi Association between telomere length in blood and mortality in people aged 60 years or older
    Richard M Cawthon
    Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA
    Lancet 361:393-5. 2003
    ..In the genetic disorder dyskeratosis congenita, telomere shortening is accelerated, and patients have premature onset of many age-related diseases and early death...
  49. ncbi DNA damage response and cellular senescence in tissues of aging mice
    Chunfang Wang
    Ageing Research Laboratories, Institute for Ageing and Health and Center for Integrated Systems Biology of Ageing and Nutrition CISBAN, Newcastle University, Newcastle upon Tyne NE4 6BE, UK
    Aging Cell 8:311-23. 2009
    ..X foci and telomeres even in crypts from very old mice, indicating that senescence in the crypt enterocytes is telomere independent. The results suggest that stress-dependent cell senescence could play a causal role for aging of mice.
  50. ncbi Cellular senescence in cancer and aging
    Manuel Collado
    Spanish National Cancer Research Center CNIO, Madrid, Spain
    Cell 130:223-33. 2007
    Cellular senescence, a state of irreversible growth arrest, can be triggered by multiple mechanisms including telomere shortening, the epigenetic derepression of the INK4a/ARF locus, and DNA damage...
  51. 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
    ..When telomeres are unmasked, genome instability arises. Balancing capping requirements with telomere replication and the enzymatic processing steps that are obligatory for telomere function is a complex problem...
  52. pmc SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin
    Eriko Michishita
    Department of Medicine, Division of Endocrinology, Gerontology and Metabolism, School of Medicine, Stanford University, Stanford, California 94305, USA
    Nature 452:492-6. 2008
    ..SIRT6 associates specifically with telomeres, and SIRT6 depletion leads to telomere dysfunction with end-to-end chromosomal fusions and premature cellular senescence...
  53. pmc Telomere length in early life predicts lifespan
    Britt J Heidinger
    College of Medical, Veterinary, and Life Sciences, Institute of Biodiversity, Animal Health, and Comparative Medicine, University of Glasgow, Glasgow G12 8QQ, United Kingdom
    Proc Natl Acad Sci U S A 109:1743-8. 2012
    ..The observed variation in telomere length among individuals of the same age is therefore thought to be related to variation in potential longevity...
  54. 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
    Human CST (CTC1-STN1-TEN1) is an RPA-like complex that is needed for efficient replication through the telomere duplex and genome-wide replication restart after fork stalling...
  55. pmc Human CST promotes telomere duplex replication and general replication restart after fork stalling
    Jason A Stewart
    Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati, OH 45267, USA
    EMBO J 31:3537-49. 2012
    Mammalian CST (CTC1-STN1-TEN1) associates with telomeres and depletion of CTC1 or STN1 causes telomere defects. However, the function of mammalian CST remains poorly understood...
  56. 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...
  57. pmc Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood
    Sonja Entringer
    Department of Pediatrics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 108:E513-8. 2011
    Leukocyte telomere length (LTL) is a predictor of age-related disease onset and mortality...
  58. ncbi ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner
    Martin J Law
    Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK
    Cell 143:367-78. 2010
    ..We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated...
  59. 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
    ..Our data identify TERRA as a telomerase ligand and natural direct inhibitor of human telomerase. Telomerase regulation by the telomere substrate may be mediated via its transcription.
  60. pmc The association of telomere length and cancer: a meta-analysis
    Ingrid M Wentzensen
    Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland 20852, USA
    Cancer Epidemiol Biomarkers Prev 20:1238-50. 2011
    ..Short telomeres in surrogate tissues (e.g., blood cells) are associated with increased cancer risk in several case-control studies, but findings are inconsistent in prospective studies...
  61. ncbi Structure of human telomeric DNA in crowded solution
    Brahim Heddi
    School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore
    J Am Chem Soc 133:9824-33. 2011
    ..These results regarding human telomeric DNA can be extended to oncogenic promoters and other genomic G-rich sequences...
  62. pmc Shortened telomere length is associated with increased risk of cancer: a meta-analysis
    Hongxia Ma
    Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
    PLoS ONE 6:e20466. 2011
    Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies...
  63. ncbi RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity
    Jean Baptiste Vannier
    DNA Damage Response Laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms, UK
    Cell 149:795-806. 2012
    ..G4) DNA structures pose a potential threat to genome stability and must be dismantled to permit efficient telomere replication...
  64. pmc Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice
    Paula Martinez
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid E 28029, Spain
    Genes Dev 23:2060-75. 2009
    The telomere repeat-binding factor 1 (TERF1, referred to hereafter as TRF1) is a component of mammalian telomeres whose role in telomere biology and disease has remained elusive...
  65. ncbi Human telomeric G-quadruplex: structures of DNA and RNA sequences
    Anh Tuân Phan
    Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore
    FEBS J 277:1107-17. 2010
    ..Such a structure might be important for telomere biology and a good target for drug design...
  66. ncbi Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging
    Elizabeth H Blackburn
    Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, MC 2200, San Francisco, California 94158 2517, USA
    Nat Med 12:1133-8. 2006
  67. pmc ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells
    Lee H Wong
    Chromosome and Chromatin Research, Murdoch Childrens Research Institute, Department of Paediatrics, University of Melbourne, Royal Children s Hospital, Parkville, Victoria 3052, Australia
    Genome Res 20:351-60. 2010
    ..3 during telomere replication at S phase...
  68. ncbi Telomere length and risk of incident cancer and cancer mortality
    Peter Willeit
    Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria
    JAMA 304:69-75. 2010
    ..Telomeres are essential to preserve the integrity of the genome. Critically short telomeres lead to replicative cell senescence and chromosomal instability and may thereby increase cancer risk...
  69. 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
    ..Indeed, telomere erosion has been documented in aging tissues and hyperproliferative disease states-conditions strongly associated ..
  70. 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
    ..identified as EST2 (ever shorter telomeres), deletion of which had independently been shown to produce telomere defects...
  71. pmc Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions
    Anitha Suram
    New Jersey Medical School University Hospital Cancer Center, UMDNJ New Jersey Medical School, Newark, NJ, USA
    EMBO J 31:2839-51. 2012
    In normal human somatic cells, telomere dysfunction causes cellular senescence, a stable proliferative arrest with tumour suppressing properties...
  72. ncbi The structures of quadruplex nucleic acids and their drug complexes
    Stephen Neidle
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Curr Opin Struct Biol 19:239-50. 2009
    ..of attention as novel anticancer targets since their formation inhibits the telomerase complex from maintaining telomere length in cancer cells...
  73. pmc Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination
    Nuno M V Gomes
    Department of Cell Biology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9039, USA
    Aging Cell 10:761-8. 2011
    Progressive telomere shortening from cell division (replicative aging) provides a barrier for human tumor progression. This program is not conserved in laboratory mice, which have longer telomeres and constitutive telomerase...
  74. ncbi Structure, location and interactions of G-quadruplexes
    Julian L Huppert
    Cavendish Laboratory, University of Cambridge, UK
    FEBS J 277:3452-8. 2010
    ..Other minireviews in this series deal with G-quadruplex nucleic acids and human disease [Wu Y & Brosh RM Jr (2010) FEBS J] and making sense of G-quadruplex and i-motif function in oncogene promoters [Brooks TA et al. (2010) FEBS J]...
  75. pmc Sub-telomere directed gene expression during initiation of invasive aspergillosis
    Andrew McDonagh
    Department of Microbiology, Imperial College London, London, United Kingdom
    PLoS Pathog 4:e1000154. 2008
    ....
  76. ncbi SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast
    S Strahl-Bolsinger
    Department of Biological Chemistry, University of California, Los Angeles 90095, USA
    Genes Dev 11:83-93. 1997
    ..can silence adjacent genes and requires RAP1, SIR2, SIR3, and SIR4 and histones H3 and H4 for this telomere position effect. SIR3 overproduction can extend the silenced domain...
  77. pmc 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility
    Nadya Dimitrova
    The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
    Nature 456:524-8. 2008
    ..To address the mechanism by which 53BP1 promotes NHEJ, we used time-lapse microscopy to measure telomere dynamics before and after their deprotection...
  78. pmc Telomeric expression sites are highly conserved in Trypanosoma brucei
    Christiane Hertz-Fowler
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
    PLoS ONE 3:e3527. 2008
    ..One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome ..
  79. pmc Histone H4 lysine 16 acetylation regulates cellular lifespan
    Weiwei Dang
    Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA
    Nature 459:802-7. 2009
    ..This pathway, distinct from existing ageing models for yeast, may represent an evolutionarily conserved function of sirtuins in regulation of replicative ageing by maintenance of intact telomeric chromatin...
  80. ncbi Mechanism of eukaryotic homologous recombination
    Joseph San Filippo
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Annu Rev Biochem 77:229-57. 2008
    ..HR is also critical for the preservation of replication forks, for telomere maintenance, and chromosome segregation in meiosis I...
  81. ncbi DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity
    Jeremy D Henson
    Children s Medical Research Institute, University of Sydney, New South Wales, Australia
    Nat Biotechnol 27:1181-5. 2009
    ..ALT) is likely to be an important target for anticancer treatment as approximately 10% of cancers depend on this telomere maintenance mechanism for continued growth, and inhibition of ALT can cause cellular senescence...
  82. pmc Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes
    Christopher M Heaphy
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Am J Pathol 179:1608-15. 2011
    Approximately 10% to 15% of human cancers lack detectable telomerase activity, and a subset of these maintain telomere lengths by the telomerase-independent telomere maintenance mechanism termed alternative lengthening of telomeres (ALT)...
  83. ncbi Coexistence of two distinct G-quadruplex conformations in the hTERT promoter
    Kah Wai Lim
    School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore
    J Am Chem Soc 132:12331-42. 2010
    The catalytic subunit of human telomerase, hTERT, actively elongates the 3' end of the telomere in most cancer cells...
  84. ncbi An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster
    Hang Yin
    Department of Cell Biology, Duke University Medical School, Durham, North Carolina 27710, USA
    Nature 450:304-8. 2007
    ..promotes euchromatic histone modifications and piRNA transcription in subtelomeric heterochromatin (also known as telomere-associated sequence, or TAS), on the right arm of chromosome 3 (3R-TAS)...
  85. 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
    ..Among the many factors that may contribute to this species variance are differences in telomere length and regulation...
  86. pmc Plasmodium falciparum heterochromatin protein 1 binds to tri-methylated histone 3 lysine 9 and is linked to mutually exclusive expression of var genes
    Karla Pérez-Toledo
    Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional IPN, Apartado Postal 14 740, 07360, Mexico D F, Mexico
    Nucleic Acids Res 37:2596-606. 2009
    ..This is the first report implicating an HP1 protein in the control of antigenic variation of a protozoan parasite...
  87. ncbi Leukocyte telomere length and cardiovascular disease in the cardiovascular health study
    Annette L Fitzpatrick
    Department of Epidemiology, School of Public Health and Community Medicine, Collaborative Health Studies Coordinating Center, University of Washington, Seattle, WA 98115, USA
    Am J Epidemiol 165:14-21. 2007
    The telomere length of replicating somatic cells is inversely correlated with age and has been reported to be associated cross-sectionally with cardiovascular disease (CVD)...
  88. ncbi BRAFE600-associated senescence-like cell cycle arrest of human naevi
    Chrysiis Michaloglou
    Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Nature 436:720-4. 2005
    ..This phenomenon, called senescence, is driven by telomere attrition, which triggers the induction of tumour suppressors including p16(INK4a) (ref. 5)...
  89. ncbi Cellular senescence in aging primates
    Utz Herbig
    Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02903, USA
    Science 311:1257. 2006
    ..Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent ..
  90. 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
    b>Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known...
  91. pmc Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings
    Owen M Wolkowitz
    Department of Psychiatry, University of California San Francisco School of Medicine, San Francisco, California, United States of America
    PLoS ONE 6:e17837. 2011
    ..Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations...
  92. ncbi Psychological and metabolic stress: a recipe for accelerated cellular aging?
    Elissa S Epel
    University of California, Department of Psychiatry, San Francisco, CA 94143, USA
    Hormones (Athens) 8:7-22. 2009
    ..environment appears to be conducive to several cell aging mechanisms, mainly dampening telomerase and leading to telomere length (TL) shortening and cell senescence...
  93. pmc Five dysfunctional telomeres predict onset of senescence in human cells
    Zeenia Kaul
    Cancer Research Unit, Children s Medical Research Institute, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia
    EMBO Rep 13:52-9. 2012
    Replicative senescence is accompanied by a telomere-specific DNA damage response (DDR). We found that DDR+ telomeres occur spontaneously in early-passage normal human cells and increase in number with increasing cumulative cell divisions...
  94. ncbi 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
    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...
  95. 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...
  96. 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
    We conducted genome-wide association analyses of mean leukocyte telomere length in 2,917 individuals, with follow-up replication in 9,492 individuals. We identified an association with telomere length on 3q26 (rs12696304, combined P = 3...
  97. pmc The parallel G-quadruplex structure of vertebrate telomeric repeat sequences is not the preferred folding topology under physiological conditions
    Robert Hänsel
    Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Max von Laue Str 9, 60438 Frankfurt Main, Germany
    Nucleic Acids Res 39:5768-75. 2011
    ..laevis egg extract or in Ficoll resembles results obtained under dilute conditions, PEG promotes the formation of high-order parallel topologies. Our data suggest that PEG should not be used as a MC mimetic...
  98. ncbi Telomere length and the risk of lung cancer
    Jin Sung Jang
    Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu 700 422, Republic of Korea
    Cancer Sci 99:1385-9. 2008
    ..We investigated the association of telomere length and the risk of lung cancer...
  99. 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
    ..These findings indicate an essential role for telomerase, and hence telomeres, in the maintenance of genomic integrity and in the long-term viability of high-renewal organ systems...
  100. ncbi The association between physical activity in leisure time and leukocyte telomere length
    Lynn F Cherkas
    Twin Research and Genetic Epidemiology Unit, King s College London, St Thomas Hospital Campus, London SE1 7EH, England
    Arch Intern Med 168:154-8. 2008
    Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging...

Research Grants71

  1. Weight Loss &Exercise Effects on Telomere Length in Postmenopausal Women
    ANNE M MCTIERNAN; Fiscal Year: 2012
    ..The telomeric regions of chromosomes comprise the molecular caps or ends of the chromosomes. Progressive telomere shortening of somatic cells with successive cell division is a hallmark of cellular aging, with loss of ~ 50-100 ..
  2. Early Life Conditions, Survival, and Health: A Pedigree-Based Population Study
    Ken R Smith; Fiscal Year: 2013
    ..hemoglobin, dehydroepiandrosterone sulfate (DHEAS &DHEA), fasting glucose and insulin resistance, telomere length, blood pressure, heart rate, grip strength, forced expiratory volume (FEV1), and BMI...
  3. OLIGOCLONAL T CELL EXPANSION AND RHEUMATOID ARTHRITIS
    Cornelia M Weyand; Fiscal Year: 2012
    ..Here, we will investigate the mechanistic links between malfunctioning of the telomere repair apparatus and mitochondrial apoptosis pathways, rendering na[unreadable]ve CD4 T cells highly sensitive to ..
  4. Mouse models of genomic instability and birth defects
    CATHERINE ELIZABETH KEEGAN; Fiscal Year: 2013
    ..a novel telomeric binding protein (also known as TPP1) that functions in a multiprotein complex to maintain telomere integrity...
  5. A novel telomerase expressing lung fibroblast phenotype
    Sem H Phan; Fiscal Year: 2012
    ..points to a potential role for telomerase in certain types of pulmonary fibrosis in humans related to reduced telomere length...
  6. Protein composition and interactions of telemeric chromatin
    Michael P Killoran; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): The terminal end or "telomere" of every linear eukaryotic chromosome is a focal point for controlling the cell's lifespan and capacity for proliferation...
  7. Herpesvirus-induced telomerase dysregulation and tumor formation
    Keith William Jarosinski; Fiscal Year: 2011
    ..Telomerase dysfunction can have tumor-promoting functions independently of net telomere elongation and maintenance of chromosomal integrity, which is consistent with the short telomeres usually present ..
  8. Regulation of EBV Latency by EBNA1
    Paul M Lieberman; Fiscal Year: 2013
    ..replication (OriP) through interactions with several host proteins important for chromosome integrity, including telomere repeat binding factors (TRFs), DNA replication pausing factors (Timeless and Tipin), and DNA recombination ..
  9. Molecular Studies of Bone Marrow Failure
    Monica Bessler; Fiscal Year: 2013
    ..classic clinical features of DC are only the "tip of the iceberg" of individuals who have BMF due to defective telomere maintenance...
  10. Characterize functions of T. brucei RAP1 and TRF in antigenic variation and telom
    Bibo Li; Fiscal Year: 2013
    ..Particularly in yeast, this telomeric silencing has been shown to depend on telomere protein RAP1...
  11. Telomere and its bio-regulators as predictors for clinical diabetes in women
    Simin Liu; Fiscal Year: 2010
    ..gradual loss of telomeric DNA in dividing somatic cells contributes to senescence and apoptosis, indicating that telomere length can be used as a critical biomarker for cell aging...
  12. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
    ..award is two-fold: 1) complete the specific aims of the research proposal, which are to determine the non-telomere roles of the CTC1-STN1-TEN1 (CST) complex in DNA replication and SCC, and 2) receive career development through ..
  13. Mouse Models of Non-Syndromic Cardiac Progeria
    Ali J Marian; Fiscal Year: 2012
    ..of senescence, namely senescence-associated 2-galactosidase (S-A 2-Gal), p16INK4a (Cdkn2a), P19, p21WAF1/CIP1, telomere attrition and telomerase activity...
  14. 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...
  15. Chromatin regulation by human SIRT7 in aging-associated cellular programs
    Katrin F Chua; Fiscal Year: 2013
    ..Cellular senescence programs are triggered by telomere dysfunction, DNA damage, activated oncogenes, and other cellular stresses in the contexts of cancer and aging...
  16. The role fo the TPP1 peotein in telomerase function and cancer cell survival
    Jayakrishnan Nandakumar; Fiscal Year: 2013
    ..These cell lines will be tested for telomere length defects and telomerase recruitment defects. 3a...
  17. RISK FACTORS FOR CVD IN WOMEN
    JOANN ELISABETH MANSON; Fiscal Year: 2012
    ..Finally, adiposity and vascular inflammation may lead to premature biological aging as measured by telomere length, with shorter telomere length associated with obesity, insulin resistance, and CHD...
  18. Defining the telomerase holoenzyme in progenitor cells with aging
    Steven E Artandi; Fiscal Year: 2013
    ..Telomerase subunits are mutated in certain human genetic diseases, such as dyskeratosis congenita, in which telomere shortening is accelerated and tissue progenitor cells are dysfunctional...
  19. Separation-of-function Mutants to Study the Biological Significance of Telomerase
    Jayakrishnan Nandakumar; Fiscal Year: 2012
    ..These cell lines will be tested for telomere length defects and telomerase recruitment defects. 3a...
  20. Suppression of genomic instability by tuning the DNA damage response at telomeres
    RACHEL L FLYNN; Fiscal Year: 2012
    ..Aim 1 will use a combination of biochemistry and cell biology to understand how the human POT1 protein protects telomere through two distinct functions...
  21. DNA-PKcs Phosphorylation on Hematopoietic Stem Cells Genome Maintenance
    Benjamin Ping Chi Chen; Fiscal Year: 2013
    ..Based on these findings, we hypothesize that the expression of the DNA-PKcs3A protein will lead to telomere dysregulation, genome instability, and carcinogenesis...
  22. Phylogenomics and functional diversification of the Heterochromatin Protein 1 gen
    MIA TAUNA LEVINE; Fiscal Year: 2012
    ..silent compartment of our genome that supports such basic cellular processes as chromosome segregation and telomere integrity...
  23. Suppression of genomic instability by tuning the DNA damage response at telomeres
    RACHEL L FLYNN; Fiscal Year: 2013
    ..Aim 1 will use a combination of biochemistry and cell biology to understand how the human POT1 protein protects telomere through two distinct functions...
  24. Determinants of Telomere Length in Chronic SCI: A Pilot Study
    Eric Garshick; Fiscal Year: 2012
    ..Previous research suggests that telomere length is reduced in association with lifestyle and clinical factors that are common in study spinal cord injury (..
  25. Role of endocrine-disrupting chemicals and social stress on perinatal outcomes
    Ami R Zota; Fiscal Year: 2012
    ..Psychosocial stress will be evaluated with subjective measures of stress and telomere length, a biomarker of cellular aging that is influenced by psychosocial stress...
  26. Astrocyte senescence and HIV-associated neurocognitive disorders
    ELIZABETH PATRICIA CROWE; Fiscal Year: 2013
    ..Senescence is classically defined as an essentially irreversible proliferative growth arrest that is telomere-based, but it can also be induced by stress...
  27. Genetic Instability &Risk for Esophageal Carcinoma
    Xifeng Wu; Fiscal Year: 2012
    ..created with institutional funds to explore the role of genetic instability using a panel of markers including telomere dysfunction and DNA damage/or repair as predictors of esophageal adenocarcinoma (EAC) risk...
  28. MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCID
    Rebecca H Buckley; Fiscal Year: 2010
    ..to produce T cells in normal number and that the T cells have a To approach this question, we plan to measure telomere length in the T cells of the various molecular types of transplants, 3) reducing the incidence of autoimmunity, ..
  29. Regulation and Function of hTERT in Human Cells
    William C Hahn; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Telomere homeostasis regulates both chromosomal stability and cell replicative lifespan in mammalian cells...
  30. 2011 Cold Spring Harbor Conference on Telomeres and Telomerase
    David J Stewart; Fiscal Year: 2010
    ..The field of telomere biology has grown rapidly once it was recognized that telomere dynamics and telomerase activation play a pivotal ..
  31. IGF-1, oxidative stress and telomere dynamics in cultured human somatic cells
    Rivka C Stone; Fiscal Year: 2012
    ..this project is to study mechanisms by which the insulin-like growth factor 1 (IGF-1) affects oxidative stress, telomere dynamics and senescence in human somatic cells...
  32. Determining the Roles of ATRX and DAXX Abnormalities in Cancer Telomere Biology
    ALAN KEITH MEEKER; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Telomeres are stabilizing elements located at the ends of the chromosomes. Telomere maintenance is central to unlimited replication - a key hallmark of the uncontrolled growth of cancer...
  33. POSTDOCTORAL TRAINING IN TUMOR BIOLOGY
    Michael L Cleary; Fiscal Year: 2013
    ..regulation;chromosomal DNA replication, repair, and recombination;cell cycle control;cancer stem cells;telomere dynamics;physiological mechanisms in normal and malignant cells;biochemical and molecular actions of oncoproteins ..
  34. Risk Factors for Ischemic Stroke in Women
    Kathryn M Rexrode; Fiscal Year: 2012
    ..Increased cellular turnover and other factors may lead to reduction in telomere length and reduced capacity for healing...
  35. Oxidative DNA base damage and repair at telomeres and the relevance to cell senes
    PATRICIA LYNN OPRESKO; Fiscal Year: 2013
    ..Oxidative stress accelerates telomere shortening, and generates reactive oxygen species (ROS), which are particularly damaging to telomeric TTAGGG ..
  36. Telomeres and lung cancer incidence and survival
    Jennifer Anne Doherty; Fiscal Year: 2013
    ..TERT is a telomere maintenance gene, and is often a site of chromosomal abnormalities in lung tumors...
  37. 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...
  38. 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...
  39. Telomere Attrition Rate and Periodontitis: a nested case control study in the ARI
    ANNE ELIZABETH SANDERS; Fiscal Year: 2013
    ..The biomarker of biological age is leukocyte telomere length (LTL) measured in genomic DNA of stored blood samples collected at Visit 2 (1990-1992) and Visit 4 (1996-..
  40. Telomere extension using nucleoside-modified mRNA and exosomes as a novel therape
    Helen M Blau; Fiscal Year: 2013
    ..Short telomere length has been linked to many diseases, including, in our labs, Duchenne muscular dystrophy (DMD) and vascular ..
  41. The Role of the Cochaperone/E3 Ubiquitin Ligase CHIP in Nuclear Stress Response
    SARAH MARIE RONNEBAUM; Fiscal Year: 2010
    ..is to identify the functional consequences of the novel interaction between CHIP and Sirtuin 6 (SirT6), a telomere-associated histone deacetylase (HDAC) that targets H3K9 and thereby inhibits NF-:B-dependent and HIF11-dependent ..
  42. Telomere Shortening and Stem Cell Maintenance
    Mary Y Armanios; Fiscal Year: 2010
    ..Telomerase is a specialized DNA polymerase responsible for telomere addition by using an intrinsic RNA template...
  43. 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 to determine if its ..
  44. Established Investigator Award in Cancer Prevention and Control
    Thomas L Vaughan; Fiscal Year: 2013
    ..ongoing and new pooled analyses with the Consortium members, including ongoing BEACON studies such as analysis of telomere length, IGF-related markers, and adipokines;as well as ancillary analyses to the ongoing genome-wide association ..
  45. Structure and dynamics of the Tetrahymena telomerase ribonucleoprotein
    Michael D Stone; Fiscal Year: 2013
    ..Telomerase catalyzes the processive extension of telomere DNA using a specialized catalytic mechanism that requires a strong functional interdependence of the telomerase ..
  46. Redefining Human Myocardial Biology
    Annarosa Leri; Fiscal Year: 2013
    ..hCSC and myocyte senescence by the expression of p53 and p16INK4a, and the accumulation of DNA damage and telomere dysfunction induced foci (TIFs) to determine the integrity of the telomere-telomerase axis;and e) The mechanical, ..
  47. Multi-Dimensional Successful Aging Among HIV-Infected Adults
    David J Moore; Fiscal Year: 2013
    ..Subjects will include 120 HIV+ adults and 90 NCs aged 36-65 years. The biomarkers will include: telomere length, F2-isoprostanes, inflammatory markers (high- sensitivity C-reactive protein, IL-6, d-dimer, TNF-alpha, ..
  48. Tumor-cell-specific targets for combined hyperthermia and radiation effects
    Tej K Pandita; Fiscal Year: 2013
    ..and absence of telomerase activity? Thus, determining the influence of heat and/or IR on ATM function and telomere metabolism will not only add to our understanding of the mechanisms of HIR but will aid in the development of new ..
  49. Telomere dysfunction, chromosome 9 instability and bladder cancer risk
    Yun Ling Zheng; Fiscal Year: 2013
    ..Chromosomal instability (CIN) is the dominant form of the genomic alterations seen in bladder tumors and telomere dysfunction may be one of the mechanisms that cause CIN...
  50. Elucidating the role of TIN2L at the telomere and in dyskeratosis congenita
    Nya D Nelson; Fiscal Year: 2013
    ..The vast majority of TINF2 mutations are de novo, and these patients have shorter telomere lengths and earlier age of disease onset in comparison to other DC patients, underscoring the severe disruption ..
  51. LIPOLYSIS AND OLEOYLETHANOLAMIDE SIGNALING IN THE REGULATION OF LONGEVITY
    ANDREW K FOLICK; Fiscal Year: 2013
    ..between obesity and signs of premature aging, such as increased prevalence of age-related disease, shortened telomere length, and reduced life-expectancy (Olshansky 2005)...
  52. MECHANISMS RESPONSIBLE FOR GENOMIC INSTABILITY IN PREMATURE AGING LAMINOPATHIES
    SUSANA GONZALO HERVAS; Fiscal Year: 2013
    ..Loss of A-type lamins leads to telomere shortening, telomeric chromatin defects, impaired DNA repair, increased genomic instability, and defects in the ..
  53. Epidemiology of lens aging in older women
    JASON LEIGH SANDERS; Fiscal Year: 2013
    ..Additionally, telomere length and interleukin-6, markers of cellular senescence and chronic inflammation, respectively, will represent ..
  54. Chronic and Acute Psychosocial Stress and Impaired Cell Aging
    Elissa S Epel; Fiscal Year: 2013
    ..Psychological stress is thought to accelerate biological aging. We found support for this hypothesis using the telomere length/telomerase maintenance system as an index of cell aging in vivo...
  55. Stress, Cellular Aging and Susceptibility to Infectious Disease
    Sheldon A Cohen; Fiscal Year: 2010
    ..The rate of cell senescence in lymphocytes (particularly in CD8 cells), as indicated by decreases in telomere length, may be an important new marker of immunocompetence and, in turn, host resistance to infectious agents...
  56. Novel Biomarkers and Causal Pathways in RA Susceptbility
    Karen H Costenbader; Fiscal Year: 2013
    ..Work by other groups has shown that telomere shortening, determined in part by genetic factors and in part by aging, smoking, systemic inflammation and ..
  57. 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...
  58. Role of endocrine-disrupting chemicals and social stress on perinatal outcomes
    Ami R Zota; Fiscal Year: 2013
    ..Psychosocial stress will be evaluated with subjective measures of stress and telomere length, a biomarker of cellular aging that is influenced by psychosocial stress...
  59. Stress, Mood, Omega-3 Fatty Acids, &Telomeric Aging: Randomized Controlled Trial
    Janice K Kiecolt-Glaser; Fiscal Year: 2012
    ..Telomeres are important for chromosomal stability and replication, and the enzyme telomerase is important for telomere formation, maintenance, and restoration...
  60. Biological Markers of System Burden in Symptomatic Knee OA: A Prospective Study
    KIMBERLY THERESA SIBILLE; Fiscal Year: 2013
    ..D., Co-Mentor, will assist with training and development in the areas of immunology, genetics, and telomere measures. Bruce McEwen, Ph.D...
  61. A Study of Telomeres in an Arsenic-Exposed Bangladesh Cohort
    BRANDON LEE PIERCE; Fiscal Year: 2013
    ..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...
  62. Stress-induced poor sleep: Sex differences, vulnerability &resilience factors
    Elissa S Epel; Fiscal Year: 2013
    ..chronic stress -- lower vagal tone, dysregulation of the HPA axis negative feedback loop, and shorter leukocyte telomere length...
  63. STRUCTURAL AND FUNCTIONAL ANALYSIS OF TELOMERASE RNAS
    Daniel Romero; Fiscal Year: 1999
    ..There is a direct correlation between the gradual shortening of telomere length in human somatic cells in vivo and in vitro with the ability of cells to divide...
  64. DNA REPLICATION AND CHROMOSOME STRUCTURE IN YEAST
    Virginia Zakian; Fiscal Year: 2009
    ..The general goal of this funding period is to understand how telomere replication is regulated in Saccharomyces. The first and major aim focuses on two helicases, Pif Ip and RrmSp...
  65. Development of a HTS Assay Targeting End Protection of Telomeres
    DEBORAH WUTTKE; Fiscal Year: 2007
    ..Protection of Telomeres 1) family of proteins, which targets the 3' single-stranded overhang region of the telomere via a specialized single-stranded DNA binding domain (DBD)...
  66. CHROMATIN-TELOMERE STRUCTURE AND AT GENOMIC SENSITIVITY
    TEJ PANDITA; Fiscal Year: 2005
    ..ATM to the TEL1 and rad3 genes of yeast, it has been suggested that mutations in the ATM could lead to defective telomere maintenance...
  67. 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...
  68. Telomerace Recruitment to Telomeres Via Core Telomore Binding Proteins
    Eladio Abreu; Fiscal Year: 2010
    ..Telomerase is the enzyme responsible for synthesizing the repetitive DNA that comprises the telomere. Our lab is primarily focusing on understanding the molecular basis for the intracellular trafficking of the core ..
  69. MECHANISMS OF FORMATION OF TERMINAL DELETIONS
    John Murnane; Fiscal Year: 2007
    ..Chromosome rearrangements associated with telomere loss and B/F/B cycles have been found in a variety of human genetic diseases, and are thought to play an ..
  70. Telomere maintenance by Werner syndrome family proteins
    FREDERICK JOHNSON; Fiscal Year: 2003
    ..b>Telomere shortening accompanies but plays an uncertain causal role in human aging...
  71. STRUCTURE AND DYNAMICS OF APTAMERS AND TELOMERE DNAS
    PHILIP BOLTON; Fiscal Year: 1999
    This research project will determine the structures and dynamics of aptamer and telomere DNAs which have quadraplex base pairing. The structure of a DNA aptamer which binds to, and inhibits thrombin has been determined...