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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Telomere

  • Moreover, elevated levels of chromosomal aberrations were detected, including telomeric end-to-end fusions, a signature of telomere dysfunction [1].
  • In successive generations of ApcMin Terc-/- mice, progressive telomere dysfunction led to an increase in initiated lesions (microscopic adenomas), yet a significant decline in the multiplicity and size of macroscopic adenomas [2].
  • These compound mutants showed increased telomere erosion and genomic instability, yet they experienced a substantial elimination of T-cell lymphomas associated with Atm deficiency [3].
  • Together, these results are consistent with the model that although telomere dysfunction provokes chromosomal aberrations that initiate carcinogenesis, telomerase-mediated telomere maintenance enables such initiated cells to efficiently achieve a fully malignant endpoint, including metastasis [4].
  • To investigate how telomerase activity and the differentiation state of germ cell tumors are related, telomerase activities and telomere lengths were measured in benign testicular tissues, germ cell cancers, and mature or immature teratomas [5].

Psychiatry related information on Telomere


High impact information on Telomere

  • Here we discuss the details of telomerase and its regulation by the telomere [9].
  • This regulation can take place at the telomere terminus, involving single-stranded DNA-binding proteins (POT1 in humans and Cdc13 in budding yeast), which have been proposed to contribute to the recruitment of telomerase and may also regulate the extent or frequency of elongation [9].
  • Telomerase is a ribonucleoprotein polymerase that specifically elongates telomeres [10].
  • A simple mechanism in which a mobile promoter moves between telomeres has been rendered unlikely by the demonstration that two telomeric transcription units can be simultaneously active when one of them is interrupted by a large DNA insertion.(ABSTRACT TRUNCATED AT 400 WORDS)[11]
  • Deletion of BUD32 or other KEOPS components leads to short telomeres and a failure to add telomeres de novo to DNA double-strand breaks [12].

Chemical compound and disease context of Telomere


Biological context of Telomere


Anatomical context of Telomere


Associations of Telomere with chemical compounds

  • Here we report physical linkage of three mouse PAR probes: DXYHgu1, DXYMov15 and (TTAGGG)n. Steroid sulphatase (Sts) maps distal to these probes, indicating that there is an internal array of the telomere sequence (TTAGGG)n in the PAR [27].
  • Single-stranded complex guanine-rich DNA sequences from chromosomal telomeres and elsewhere can associate to form stable parallel four-stranded structures termed G4-DNA by a process that is anomalously dependent on the particular alkali metal cation that is present [28].
  • Here we report that histone H3 is required for full repression at yeast telomeres and at partially disabled silent mating loci, and that the acetylatable lysine residues of H3 play an important role in silencing [29].
  • Mutations in the conserved acetyl-CoA binding motif of Sas2p are shown to disrupt the ability of Sas2p to mediate the silencing at HML and telomeres, providing evidence for an important role for the acetyltransferase activity of the SAS complex in silencing [30].
  • The B. burgdorferi telomere resolvase ResT generates the hairpin telomeres from replication intermediates in a reaction with mechanistic similarities to that catalyzed by type IB topoisomerases and tyrosine recombinases [31].

Gene context of Telomere

  • Moreover, telomerase inhibition in human tumour cell lines using dominant-negative versions of TERT leads to telomere shortening and cell death [32].
  • Immunofluorescence studies with antibodies against RAP1 and SIR3 demonstrate that the H3 and H4 N-termini are required for the association of SIR3 with telomeric chromatin and the perinuclear positioning of yeast telomeres [33].
  • In addition, normal telomere length can be restored by expressing a Cdc13-Est1p hybrid protein [34].
  • Accompanying the continual telomere shortening, the growth rate of Terc-deficient ES cells was gradually reduced after more than 300 divisions [24].
  • MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks [35].

Analytical, diagnostic and therapeutic context of Telomere


  1. Telomere maintenance requires the RAD51D recombination/repair protein. Tarsounas, M., Muñoz, P., Claas, A., Smiraldo, P.G., Pittman, D.L., Blasco, M.A., West, S.C. Cell (2004) [Pubmed]
  2. Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Rudolph, K.L., Millard, M., Bosenberg, M.W., DePinho, R.A. Nat. Genet. (2001) [Pubmed]
  3. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Wong, K.K., Maser, R.S., Bachoo, R.M., Menon, J., Carrasco, D.R., Gu, Y., Alt, F.W., DePinho, R.A. Nature (2003) [Pubmed]
  4. Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression. Chang, S., Khoo, C.M., Naylor, M.L., Maser, R.S., DePinho, R.A. Genes Dev. (2003) [Pubmed]
  5. Telomerase activity in germ cell cancers and mature teratomas. Albanell, J., Bosl, G.J., Reuter, V.E., Engelhardt, M., Franco, S., Moore, M.A., Dmitrovsky, E. J. Natl. Cancer Inst. (1999) [Pubmed]
  6. Non-random association between alleles detected at D4S95 and D4S98 and the Huntington's disease gene. Theilmann, J., Kanani, S., Shiang, R., Robbins, C., Quarrell, O., Huggins, M., Hedrick, A., Weber, B., Collins, C., Wasmuth, J.J. J. Med. Genet. (1989) [Pubmed]
  7. Tissue-specific alternate splicing of human telomerase reverse transcriptase (hTERT) influences telomere lengths during human development. Ulaner, G.A., Hu, J.F., Vu, T.H., Giudice, L.C., Hoffman, A.R. Int. J. Cancer (2001) [Pubmed]
  8. Analysis of large and small colony L5178Y tk-/- mouse lymphoma mutants by loss of heterozygosity (LOH) and by whole chromosome 11 painting: detection of recombination. Liechty, M.C., Scalzi, J.M., Sims, K.R., Crosby, H., Spencer, D.L., Davis, L.M., Caspary, W.J., Hozier, J.C. Mutagenesis (1998) [Pubmed]
  9. Regulation of telomerase by telomeric proteins. Smogorzewska, A., de Lange, T. Annu. Rev. Biochem. (2004) [Pubmed]
  10. Telomere length regulation. Greider, C.W. Annu. Rev. Biochem. (1996) [Pubmed]
  11. Discontinuous transcription and antigenic variation in trypanosomes. Borst, P. Annu. Rev. Biochem. (1986) [Pubmed]
  12. A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator. Downey, M., Houlsworth, R., Maringele, L., Rollie, A., Brehme, M., Galicia, S., Guillard, S., Partington, M., Zubko, M.K., Krogan, N.J., Emili, A., Greenblatt, J.F., Harrington, L., Lydall, D., Durocher, D. Cell (2006) [Pubmed]
  13. Phage N15 telomere resolution. Target requirements for recognition and processing by the protelomerase. Deneke, J., Ziegelin, G., Lurz, R., Lanka, E. J. Biol. Chem. (2002) [Pubmed]
  14. Prostate cancer is characterized by epigenetic silencing of 14-3-3sigma expression. Lodygin, D., Diebold, J., Hermeking, H. Oncogene (2004) [Pubmed]
  15. Prevention of critical telomere shortening by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis. Sato, R., Maesawa, C., Fujisawa, K., Wada, K., Oikawa, K., Takikawa, Y., Suzuki, K., Oikawa, H., Ishikawa, K., Masuda, T. Gut (2004) [Pubmed]
  16. Tumour-cell apoptosis after cisplatin treatment is not telomere dependent. Jeyapalan, J.C., Saretzki, G., Leake, A., Tilby, M.J., von Zglinicki, T. Int. J. Cancer (2006) [Pubmed]
  17. A novel platinum compound inhibits telomerase activity in vitro and reduces telomere length in a human hepatoma cell line. Furuta, M., Nozawa, K., Takemura, M., Izuta, S., Murate, T., Tsuchiya, M., Yoshida, K., Taka, N., Nimura, Y., Yoshida, S. Int. J. Cancer (2003) [Pubmed]
  18. Homologous recombination generates T-loop-sized deletions at human telomeres. Wang, R.C., Smogorzewska, A., de Lange, T. Cell (2004) [Pubmed]
  19. Telomerase maintains telomere structure in normal human cells. Masutomi, K., Yu, E.Y., Khurts, S., Ben-Porath, I., Currier, J.L., Metz, G.B., Brooks, M.W., Kaneko, S., Murakami, S., DeCaprio, J.A., Weinberg, R.A., Stewart, S.A., Hahn, W.C. Cell (2003) [Pubmed]
  20. Erosion of the telomeric single-strand overhang at replicative senescence. Stewart, S.A., Ben-Porath, I., Carey, V.J., O'Connor, B.F., Hahn, W.C., Weinberg, R.A. Nat. Genet. (2003) [Pubmed]
  21. Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Weinrich, S.L., Pruzan, R., Ma, L., Ouellette, M., Tesmer, V.M., Holt, S.E., Bodnar, A.G., Lichtsteiner, S., Kim, N.W., Trager, J.B., Taylor, R.D., Carlos, R., Andrews, W.H., Wright, W.E., Shay, J.W., Harley, C.B., Morin, G.B. Nat. Genet. (1997) [Pubmed]
  22. Loss of a yeast telomere: arrest, recovery, and chromosome loss. Sandell, L.L., Zakian, V.A. Cell (1993) [Pubmed]
  23. Telomere maintenance by recombination in human cells. Dunham, M.A., Neumann, A.A., Fasching, C.L., Reddel, R.R. Nat. Genet. (2000) [Pubmed]
  24. Severe growth defect in mouse cells lacking the telomerase RNA component. Niida, H., Matsumoto, T., Satoh, H., Shiwa, M., Tokutake, Y., Furuichi, Y., Shinkai, Y. Nat. Genet. (1998) [Pubmed]
  25. Accelerated telomere shortening in ataxia telangiectasia. Metcalfe, J.A., Parkhill, J., Campbell, L., Stacey, M., Biggs, P., Byrd, P.J., Taylor, A.M. Nat. Genet. (1996) [Pubmed]
  26. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Morin, G.B. Cell (1989) [Pubmed]
  27. High frequency de novo alterations in the long-range genomic structure of the mouse pseudoautosomal region. Kipling, D., Salido, E.C., Shapiro, L.J., Cooke, H.J. Nat. Genet. (1996) [Pubmed]
  28. A sodium-potassium switch in the formation of four-stranded G4-DNA. Sen, D., Gilbert, W. Nature (1990) [Pubmed]
  29. Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast. Thompson, J.S., Ling, X., Grunstein, M. Nature (1994) [Pubmed]
  30. The yeast SAS (something about silencing) protein complex contains a MYST-type putative acetyltransferase and functions with chromatin assembly factor ASF1. Osada, S., Sutton, A., Muster, N., Brown, C.E., Yates, J.R., Sternglanz, R., Workman, J.L. Genes Dev. (2001) [Pubmed]
  31. Fusion of hairpin telomeres by the B. burgdorferi telomere resolvase ResT implications for shaping a genome in flux. Kobryn, K., Chaconas, G. Mol. Cell (2005) [Pubmed]
  32. Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. González-Suárez, E., Samper, E., Flores, J.M., Blasco, M.A. Nat. Genet. (2000) [Pubmed]
  33. Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast. Hecht, A., Laroche, T., Strahl-Bolsinger, S., Gasser, S.M., Grunstein, M. Cell (1995) [Pubmed]
  34. RPA regulates telomerase action by providing Est1p access to chromosome ends. Schramke, V., Luciano, P., Brevet, V., Guillot, S., Corda, Y., Longhese, M.P., Gilson, E., Géli, V. Nat. Genet. (2004) [Pubmed]
  35. MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks. Mills, K.D., Sinclair, D.A., Guarente, L. Cell (1999) [Pubmed]
  36. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Zhu, X.D., Küster, B., Mann, M., Petrini, J.H., de Lange, T. Nat. Genet. (2000) [Pubmed]
  37. Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Meneghini, M.D., Wu, M., Madhani, H.D. Cell (2003) [Pubmed]
  38. Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae. Tsukamoto, Y., Kato, J., Ikeda, H. Nature (1997) [Pubmed]
  39. Subnuclear shuttling of human telomerase induced by transformation and DNA damage. Wong, J.M., Kusdra, L., Collins, K. Nat. Cell Biol. (2002) [Pubmed]
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