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Runaway telomere elongation caused by telomerase RNA gene mutations

Abstract

The ribonucleoprotein enzyme telomerase adds telomeric DNA onto chromosome ends and is normally regulated so that telomeric DNA lengths are kept within defined bounds. In the telomerase RNA gene from the yeast Kluyveromyces lactis, specific mutations that alter telomeric DNA sequences result in telomeres elongating to up to 100 times their normal length and impair cell growth. Some mutations cause immediate elongation whereas others behave like genetic time bombs, causing elongation only after a latent period of hundreds of generations.

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References

  1. Blackburn, E. H. Cell 77, 621–623 (1994).

    Article  CAS  Google Scholar 

  2. Blackburn, E. H. A. Rev. Biochem. 61, 113–129 (1992).

    Article  CAS  Google Scholar 

  3. Pardue, M. L. Curr. Opin. genet. Dev. 4, 845–850 (1994).

    Article  CAS  Google Scholar 

  4. Greider, C. W. & Blackburn, E. H. Nature 337, 331–337 (1989).

    Article  ADS  CAS  Google Scholar 

  5. Shippen, L. D. & Blackburn, E. H. Science 247, 546–552 (1990).

    Article  ADS  Google Scholar 

  6. Greider, C. W. Molec. cell. Biology 11, 4572–4580 (1991).

    Article  CAS  Google Scholar 

  7. Harrington, L. A. & Greider, C. W. Nature 353, 451–454 (1991).

    Article  ADS  CAS  Google Scholar 

  8. Lee, M. & Blackburn, E. H. Molec. cell Biol. 13, 6586–6599 (1993).

    Article  CAS  Google Scholar 

  9. Shippen, D. E., Blackburn, E. H. & Price, C. M. Proc. natn. Acad. Sci. U.S.A. 91, 405–409 (1994).

    Article  ADS  CAS  Google Scholar 

  10. Harley, C. B., Futcher, A. B. & Greider, C. W. Nature 345, 458–460 (1990).

    Article  ADS  CAS  Google Scholar 

  11. Hastie, N. D. et al. Nature 346, 866–868 (1990).

    Article  ADS  CAS  Google Scholar 

  12. Morin, G. B. Cell 59, 521–529 (1989).

    Article  CAS  Google Scholar 

  13. Prowse, K. R., Avilion, A. A. & Greider, C. W. Proc. natn. Acad. Sci. U.S.A. 90, 1493–1497 (1993).

    Article  ADS  CAS  Google Scholar 

  14. Shay, J. W., Wright, W. E., Brasiskyte, D. & van der Hagen, B. A. Oncogene 8, 1407–1413 (1993).

    CAS  PubMed  Google Scholar 

  15. Counter, C. M., Hirte, H. W., Bacchetti, S. & Harley, C. B. Proc. natn. Acad. Sci. U.S.A. 91, 2900–2904 (1994).

    Article  ADS  CAS  Google Scholar 

  16. Klingerhutz, A. J., Barber, S., Smith, P. P., Dyer, K. & McDougall, J. K. Molec. cell. Biol. 14, 961–969 (1994).

    Article  Google Scholar 

  17. Blackburn, E. H. Nature 350, 569–573 (1991).

    Article  ADS  CAS  Google Scholar 

  18. Zakian, V. A. Rev. Genet. 23, 579–604 (1989).

    Article  CAS  Google Scholar 

  19. Shampay, J. & Blackburn, E. H. Proc. natn. Acad. Sci. U.S.A. 85, 534–538 (1988).

    Article  ADS  CAS  Google Scholar 

  20. Runge, K. W. & Zakian, V. A. Molec cell Biol. 9, 1488–1497 (1989).

    Article  CAS  Google Scholar 

  21. Berman, J., Tachibana, C. Y. & Tye, B.-K. Proc. natn. Acad. Sci. U.S.A. 83, 3713–3717 (1986).

    Article  ADS  CAS  Google Scholar 

  22. Conrad, M. N., Wright, J. H., Wolf, A. J. & Zakian, V. A. Cell 63, 739–750 (1990).

    Article  CAS  Google Scholar 

  23. Kyrion, G., Boakye, K. A. & Lustig, A. J. Molec. cell. Biol. 12, 5159–5173 (1992).

    Article  CAS  Google Scholar 

  24. McEachern, M. J. & Blackburn, E. H. Proc. natn. Acad. Sci. U.S.A. 91, 3453–3457 (1994).

    Article  ADS  CAS  Google Scholar 

  25. McEachern, M. J. & Hicks, J. B. Molec. cell. Biol. 13, 551–560 (1993).

    Article  CAS  Google Scholar 

  26. Lundblad, V. & Szostak, J. W. Cell 57, 633–643 (1989).

    Article  CAS  Google Scholar 

  27. Singer, M. S. & Gottschling, D. E. Science 266, 404–409 (1994).

    Article  ADS  CAS  Google Scholar 

  28. Lundblad, V. & Blackburn, E. H. Cell 73, 347–360 (1993).

    Article  CAS  Google Scholar 

  29. Yu, G.-L., Bradley, J. D., Attardi, L. D. & Blackburn, E. H. Nature 344, 126–132 (1990).

    Article  ADS  CAS  Google Scholar 

  30. Henderson, E., Hardin, C. C., Walk, S. K., Tinoco, I. J. & Blackburn, E. H. Cell 51, 899–908 (1987).

    Article  CAS  Google Scholar 

  31. Sundquist, W. I. & Klug, A. Nature 342, 825–829 (1989).

    Article  ADS  CAS  Google Scholar 

  32. Veselkov, A. G., Malkov, V. A., Frank-Kamenetskii, M. D. & Dobrynin, V. N. Nature 364, 496 (1993).

    Article  ADS  CAS  Google Scholar 

  33. Williamson, J. R. Rev. Biophys. biomol. Struct. 23, 703–730 (1994).

    Article  CAS  Google Scholar 

  34. Gottschling, D. E. & Zakian, V. A. Cell 47, 195–205 (1986).

    Article  CAS  Google Scholar 

  35. Price, C. M. & Cech, T. R. Biochemistry 28, 769–774 (1989).

    Article  CAS  Google Scholar 

  36. Lustig, A. J., Kurtz, S. & Shore, D. Science 250, 549–553 (1990).

    Article  ADS  CAS  Google Scholar 

  37. Larson, G. P., Castanotto, D., Rossi, J. J. & Malafa, M. P. Gene 150, 35–41 (1994).

    Article  CAS  Google Scholar 

  38. Gottschling, D. E., Aparicio, O. M., Billington, B. L. & Zakian, V. A. Cell 63, 751–762 (1990).

    Article  CAS  Google Scholar 

  39. Köhrer, K. & Domdey, H. Meth. Enzym. 194, 398–405 (1991).

    Article  Google Scholar 

  40. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1989).

    Google Scholar 

  41. Wray, L. V., Witte, M. M., Dickson, R. C. & Riley, M. I. Molec. cell Biol. 7, 1111–1121 (1987).

    Article  CAS  Google Scholar 

  42. Sikorski, R. S. & Boeke, J. D. Meth. Enzym. 194, 302–318 (1991).

    Article  CAS  Google Scholar 

  43. Church, G. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 81, 1991–1995 (1984).

    Article  ADS  CAS  Google Scholar 

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McEachern, M., Blackburn, E. Runaway telomere elongation caused by telomerase RNA gene mutations. Nature 376, 403–409 (1995). https://doi.org/10.1038/376403a0

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