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Interaction between Set1p and checkpoint protein Mec3p in DNA repair and telomere functions

Nature Genetics volume 21, pages 204–208 (1999)Cite this article

Abstract

The yeast protein Set1p, inactivation of which alleviates telomeric position effect (TPE), contains a conserved SET domain present in chromosomal proteins involved in epigenetic control of transcription1,2. Mec3p is required for efficient DNA–damage–dependent checkpoints at G1/S, intra–S and G2/M (refs 3, 4,5,6 and 7). We show here that the SET domain of Set1p interacts with Mec3p. Deletion of SET1 increases the viability of mec3Δ mutants after DNA damage (in a process that is mostly independent of Rad53p kinase, which has a central role in checkpoint control8,9) but does not significantly affect cell–cycle progression. Deletion of MEC3 enhances TPE and attenuates the set1Δ–induced silencing defect. Furthermore, restoration of TPE in a set1Δ mutant by overexpression of the isolated SET domain requires Mec3p. Finally, deletion of MEC3 results in telomere elongation, whereas cells with deletions of both SET1 and MEC3 do not have elongated telomeres. Our findings indicate that interactions between SET1 and MEC3 have a role in DNA repair and telomere function.

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Figure 1: Interaction of the SET domain with Mec3p.
Figure 2: The set1Δ1 mutation partially rescues ultraviolet and γ–ray sensitivity of checkpoint mutant strains.
Figure 3: Analysis of G1 and G2 DNA–damage checkpoints.
Figure 4: Mec3p reduces TPE.
Figure 5: Mec3p and Set1p regulate telomere length in opposite directions.

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Acknowledgements

We thank P. Moreau, R. Brent, M. Djabali, M. Cockell, S. Gasser, M. Bolotin, M. Kazmaier, P. Linder, D. Gottschling, C. Mann, C. Fairhead, C. Nislow, L. Pillus, M. Bickle, G. Georgiou, P. Luciano, G. Fourel, S. Marcand and A. Rigal for discussions, protocols and materials; S. Gasser, M. Cockell, C. Mann, G. Schatz, G. Lucchini and G. Cavalli for their suggestions and corrections; and M. Zalewski for technical assistance. Work in the laboratories of V.G. and E.G. was supported by La Ligue Nationale contre le Cancer and l'Association pour la Recherche sur le Cancer. Work in the laboratory of M.P. is supported by Grant MURST Cofinanz. Progr. di Ricerca di Interesse nazionale 1997.

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  1. Yves Corda and Vera Schramke: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratoire d'Ingénierie et de Dynamique des Systèmes Macromoléculaires, CNRS, 31 chemin joseph Aiguier, Marseille, Cedex 20, 13402, France

    Yves Corda, Vera Schramke, Tamara Smokvina & Vincent Géli

  2. Dipartimento di Genetica e di Biologia dei Microrganismi, Università degli Studi di Milano, Via Celoria 26, Milano, 20133, Italy

    Maria Pia Longhese & Vera Paciotti

  3. Laboratoire de Biologie Cellulaire et Moléculaire CNRS, UMR 8510, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, Lyon Cedex, 69364, France

    Vanessa Brevet & Eric Gilson

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Correspondence to Vincent Géli.

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Corda, Y., Schramke, V., Longhese, M. et al. Interaction between Set1p and checkpoint protein Mec3p in DNA repair and telomere functions. Nat Genet 21, 204–208 (1999). https://doi.org/10.1038/5991

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