CoChat
Sign Up
Cited by 205

hTERT associates with human telomeres and enhances genomic stability and DNA repair

Sharma, Girdhar G, Gupta, Arun, Wang, Huichen, Scherthan, Harry, Dhar, Sonu, Gandhi, Varsha, Iliakis, George, Shay, Jerry W, Young, Charles S H, Pandita, Tej K·2003·Oncogene
DOI 10.1038/sj.onc.1206063
Open this paper in CoChat — free account

Abstract

Ectopic expression of telomerase in telomerase-silent cells is sufficient to overcome senescence and to extend cellular lifespan. We show here that the catalytic subunit of human telomerase (hTERT) crosslinks telomeres. This interaction is blocked by the telomere repeat binding factor 1, but not by a dominant negative form of this protein. It is also abolished by destruction of the RNA component of telomerase as well as by mutations in the hTERT protein. Ectopic expression of hTERT leads to transcriptional alterations of a subset of genes and changes in the interaction of the telomeres with the nuclear matrix. This is associated with reduction of spontaneous chromosome damage in G(1) cells, enhancement of the kinetics of DNA repair and an increase in NTP levels. The effect on DNA repair is likely indirect as TERT does not directly affect DNA end rejoining in vitro or meiotic recombination in vivo. The observed effects of hTERT occurred rapidly before any significant lengthening of telomeres was observed. Our findings establish an intimate relationship between hTERT-telomere interactions and alteration in transcription of a subset of genes that may lead to increased genomic stability and enhanced repair of genetic damage. These novel functions of telomerase are distinct from its known effect on telomere length and have potentially important biological consequences.

Overview

Integrity signals

Registry

Crossref · 10.1038/sj.onc.1206063

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The increase in telomere length in quiescent/differentiated tissues could be related to prevention of stress-dependent telomere shortening.

    “The increase in telomere length in quiescent/differentiated tissues could be related to prevention of stress-dependent telomere shortening (Sahin et al, 2011; Sharma et al, 2003), or to re-population of tissues by cells with longer telomeres (Hao et al, 2005).”

    From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Sharma et al, 2003

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 53

  1. Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB, Greider CW and Harley CB . (1992). Proc. Natl. Acad. Sci. USA, 89, 10 114–10 118. · DOI · Paper page
  2. Baur JA, Zou Y, Shay JW and Wright WE . (2001). Science, 292, 2075–2077. · DOI
  3. Blackburn EH . (2001). Cell, 106, 661–673. · DOI
  4. Braunstein M, Rose AB, Holmes SG, Allis CD and Broach JR . (1993). Genes Dev., 7, 592–604. · DOI
  5. Chan SW and Blackburn EH . (2002). Oncogene, 21, 553–563. · DOI
  6. Choi D, Whittier PS, Oshima J and Funk WD . (1997). FASEB J., 15, 1014–1020. · DOI
  7. Constantinou A, Davies AA and West SC . (2001). Cell. 104, 259–268. · DOI
  8. Dhar S, Squire JA, Hande MP, Wellinger RJ and Pandita TK . (2000). Mol. Cell. Biol., 20, 7764–7772. · DOI
  9. Etheridge KT, Banik SSR, Armbruster BN, Zhy Y, Terns RM, Terns MP and Counter CM . (2002). J. Biol. Chem., 277, 24764–24770. · DOI
  10. Fan Z, Chakravarty P, Alfieri A, Pandita TK, Vikram B and Guha C . (2000). Cancer Gene Ther., 7, 1307–1314. · DOI
  11. Ford PP, Suh JM, Wright WE and Shay JW . (2000). Mol. Cell Biol., 20, 9084–9091. · DOI
  12. Fu W, Killen M, Culmsee C, Dhar S, Pandita TK and Mattson MP . (2000). J. Mol. Neurosci., 14, 3–15. · DOI
  13. Gottschling DE, Aparicio OM, Billington BL and Zakian VA . (1990). Cell, 63, 751–762. · DOI
  14. Goytisolo FA, Samper E, Martin-Caballero J ., Finnon P, Herrera E ., Flores JM, Bouffler SD and Blasco MA . (2000). J. Exp. Med., 192, 1625–1636. · DOI
  15. Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK and Allshire RC . (1990). Nature, 346, 866–868. · DOI · Paper page
  16. Hsu HL, Gilley D, Blackburn EH and Chen DJ . (1999). Proc. Natl. Acad. Sci. USA, 96, 12 454–12 458. · DOI
  17. Iliakis G, Wang Y and Wang HY . (1999). Methods Mol. Biol., 113, 543–553. · DOI
  18. Johnson RT and Rao PN . (1970). Nature, 226, 717–722. · DOI
  19. Kawakaim Y, Kitamoto M, Nakanishi T, Yasui W, Tahara E, Nakayama J, Ishikawa F, Tahara H, Ide T and Kajiyama G . (2000). Oncogene, 19, 3888–3893. · DOI
  20. Kharbanda S, Kumar V, Dhar S, Pandey P, Chen C, Majumder P, Yuan ZM, Whang Y, Strauss W, Pandita TK, Weaver D and Kufe D . (2000). Curr. Biol., 10, 568–575. · DOI
  21. Kondo S, Kondo Y, Li G, Silverman RH and Cowell JK . (1998). Oncogene, 16, 3323–3330. · DOI
  22. Krude T and Keller C . (2001). Cell Mol. Life Sci., 58, 665–672. · DOI
  23. Kyrion G, Liu K, Liu C and Lustig AJ . (1993). Genes Dev. 7, 1146–1159. · DOI
  24. Levy MZ, Allsopp RC, Futcher AB, Greider CW and Harley CB . (1992). J. Mol. Biol., 225, 951–960. · DOI · Paper page
  25. Liu Y, Snow BE, Hande MP, Yeung D, Erdmann NJ, Wakeham A, Itie A, Siderovski DP, Lansdorp PM, Robinson MO and Harrington L . (2000). Curr. Biol., 10, 1459–1462. · DOI · Paper page
  26. Luderus ME, van Steensel B, Chong L, Sibon OC, Cremers FF and de Lange T . (1996). J. Cell Biol., 135, 867–881. · DOI
  27. Martin-Rivera L, Herrera E, Albar JP and Blasco MA . (1998). Proc. Natl. Acad. Sci. USA, 95, 10 471–10 476. · DOI
  28. Ng P, Cummings DT, Evelegh CM and Graham FL . (2000). Biotechniques, 29, 524–526. · DOI
  29. Ouellette MM, McDaniel LD, Wright WE, Shay JW and Schultz RA . (2000). Hum. Mol. Genet., 9, 403–411. · DOI
  30. Pandita TK and Hittelman WN . (1992). Radiat. Res., 130, 94–103. · DOI
  31. Pandita TK, Gregoire V, Dhingra K and Hittelman WN . (1994). Cytogenet. Cell. Genet., 67, 94–101. · DOI
  32. Pandita TK, Pathak S and Geard CR . (1995). Cytogenet. Cell Genet., 71, 86–93. · DOI
  33. Pandita TK, Westphal CH, Anger M, Sawant SG, Geard CR, Pandita RK and Scherthan H . (1999). Mol. Cell Biol., 19, 5096–5105. · DOI
  34. Pommier Y, Schwartz RE, Zwelling LA and Kohn KW . (1985). Biochemistry, 24, 6406–6410. · DOI
  35. Renauld H, Aparicio OM, Zierath PD, Billington BL, Chhablani SK and Gottschling DE . (1993). Genes Dev., 7, 1133–1145. · DOI
  36. Roberts JJ . (1978). Adv. Radiat. Biol., 7, 211–435. · DOI
  37. Rodriguez Jr CO, Plunkett W, Paff MT, Du M, Nowak B, Ramakrishna P, Keating MJ and Gandhi V . (2000). J. Chromatogr. B. Biomed. Sci. Appl., 745, 421–430. · DOI
  38. Rudd GN, Hartley JA and Souhami RL . (1995). Cancer Chemother. Pharmacol., 35, 323–326. · DOI
  39. Sawant SG, Gregoire V, Dhar S, Umbricht CB, Cvilic S, Sukumar S and Pandita TK . (1999). FASEB J., 13, 1047–1054. · DOI
  40. Scherthan H . (2001). Nat. Rev. Mol. Cell Biol., 2, 621–627. · DOI
  41. Scherthan H, Jerratsch M, Dhar S, Wang YA, Goff SP and Pandita TK . (2000). Mol. Cell Biol., 20, 7773–7783. · DOI
  42. Sherman PA and Fyfe JA . (1989). Anal. Biochem., 180, 222–226. · DOI
  43. Smilenov LB, Dhar S and Pandita TK . (1999). Mol. Cell Biol., 19, 6963–6971. · DOI
  44. Smith S and de Lange T . (1997). Trends Genet., 13, 21–26. · DOI
  45. Steinert S, Shay JW and Wright WE . (2000). Biochem. Biophys. Res. Commun., 273, 1095–1098. · DOI
  46. Tahara H, Yasui W, Tahara E, Fujimoto J, Ito K, Tamai K, Nakayama J, Ishikawa F, Tahara E and Ide T . (1999). Oncogene, 18, 1561–1567. · DOI
  47. Vafa O, Wade M, Kern S, Beeche M, Pandita TK, Hampton GM and Wahl GM . (2002). Mol. Cell, 9, 1031–1044. · DOI · Paper page
  48. Van Komen S, Petukhova G, Sigurdsson S, Stratton S and Sung P . (2000). Mol. Cell, 6, 563–572. · DOI
  49. Vaziri H, Squire JA, Pandita TK, Bradley G, Kuba RM, Zhang H, Gulyas S, Hill RP, Nolan GP and Benchimol S . (1999). Mol. Cell Biol., 19, 2373–2379. · DOI
  50. Vaziri H, West MD, Allsopp RC, Davison TS, Wu YS, Arrowsmith CH, Poirier GG and Benchimol S . (1997). EMBO J., 16, 6018–6033. · DOI
  51. Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, Bodnar AG, Lichtsteiner S, Kim NW, Trager JB, Taylor RD, Carlos R, Andrews WH, Wright WE, Shay JW, Harley CB and Morin GB . (1997). Nat. Genet., 17, 498–502. · DOI
  52. Wright WE and Shay JW . (1992). Trends Genet. 8, 193–197. · DOI
  53. Zhang X, Mar V, Zhou W, Harrington L and Robinson MO . (1999). Genes Dev. 13, 2388–2399. · DOI · Paper page

Cited by

Sorted by citations

Metadata

Authors
Sharma, G. G., Gupta, A., Wang, H., Scherthan, H., Dhar, S., Gandhi, V., Iliakis, G., Shay, J. W., Young, C. S. H., & Pandita, T. K.
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2003-01-09
Volume
22
Issue
1
Pages
131-146
ISSN
  • 0950-9232
  • 1476-5594
DOI
10.1038/sj.onc.1206063
Cited by
205
References
12
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review