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  • The EMBO Journal (2003) 22, 1697 - 1706
  • doi:10.1093/emboj/cdg155

The number of vertebrate repeats can be regulated at yeast telomeres by Rap1-independent mechanisms

Vanessa Brevet1, Anne-Sophie Berthiau1, Livia Civitelli2, Pierluigi Donini2, Vera Schramke3, Vincent Géli3, Fiorentina Ascenzioni2 and Eric Gilson1

  1. Laboratoire de Biologie Moléculaire de la Cellule, UMR5665, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France
  2. Istituto Pasteur-Fondazione Cenci Bolognetti, c/o Dipartimento di Biologia Cellulare e dello Sviluppo, University of Rome 'La Sapienza', via dei Sardi 70, 00185 Rome, Italy
  3. Laboratoire d'Ingénierie et de Dynamique des Systèmes Macromoléculaires, CNRS, 31 chemin Joseph Aiguier, 13402 Marseille Cedex 20, France

Correspondence to:

Eric Gilson, E-mail: Eric.Gilson@ens-lyon.fr

Received 18 November 2002; Accepted 12 February 2003; Revised 22 January 2003

The number of telomeric DNA repeats at chromosome ends is maintained around a mean value by a dynamic balance between elongation and shortening. In particular, proteins binding along the duplex part of telomeric DNA set the number of repeats by progressively limiting telomere growth. The paradigm of this counting mechanism is the Rap1 protein in Saccharomyces cerevisiae. We demonstrate here that a Rap1-independent mechanism regulates the number of yeast telomeric repeats (TG1–3) and of vertebrate repeats (T2AG3) when TEL1, a yeast ortholog of the human gene encoding the ATM kinase, is inactivated. In addition, we show that a T2AG3-only telomere can be formed and maintained in humanized yeast cells carrying a template mutation of the gene encoding the telomerase RNA, which leads to the synthesis of vertebrate instead of yeast repeats. Genetic and biochemical evidences indicate that this telomere is regulated in a Rap1-independent manner, both in TEL1 and in tel1Delta humanized yeast cells. Altogether, these findings shed light on multiple repeat-counting mechanisms, which may share critical features between lower and higher eukaryotes.

  • Keywords:

    • evolution,
    • TEL1,
    • telomerase,
    • telomere,
    • yeast