Abstract
ATM/ATR homologs are the central elements of genome surveillance mechanisms in many organisms, including yeasts, flies, and mammals. In Saccharomyces cerevisiae, most checkpoint responses depend on the ATR ortholog Mec1p. The yeast ATM ortholog, Tel1p, so far has been implicated in a specific DNA damage checkpoint during S-phase as well as in telomere homeostasis. In particular, yeast cells lacking only Tel1p harbor short but stable telomeres, while cells lacking both Tel1p and Mec1p are unable to maintain telomeric repeats and senesce. Here, we present the characterization of a new mutation in the TEL1-gene, called tel1-11, which was isolated by virtue of a synthetic lethal interaction at 37°C with a previously described mec1-ts mutation. Interestingly, telomere and checkpoint functions are differentially affected by the mutant protein Tel1-11p. The Tel1p-dependent checkpoint response is undetectable in cells containing Tel1-11p and incubated at 37°C, but basic telomere function is maintained. Further, when the same cells are incubated at 26°C, Tel1-11p confers full proficiency for all telomere functions analyzed, whereas the function for DNA-damage checkpoint activation is clearly affected. The results thus strongly suggest that the different cellular pathways affected by Tel1p do not require the same level of Tel1p activity to be fully functional.
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Acknowledgements
We thank R. Rothstein, D. Durocher, T. Weinert, and M. -P. Longhese for generously providing yeast strains, plasmid constructs, or antibodies used in this study. This project was actually initiated by I. Dionne, whom we thank for providing unpublished data. The work was supported by the Canadian Cancer Society (NCIC research grant 013235). M. C. was supported by a postdoctoral fellowship by the Swiss National Science Fund and R. J. W. is a Chercheur National from the FRSQ.
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Chakhparonian, M., Faucher, D. & Wellinger, R.J. A mutation in yeast Tel1p that causes differential effects on the DNA damage checkpoint and telomere maintenance. Curr Genet 48, 310–322 (2005). https://doi.org/10.1007/s00294-005-0020-7
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DOI: https://doi.org/10.1007/s00294-005-0020-7