Abstract
Proteins involved in telomere end protection have previously been identified. In Saccharomyces cerevisiae, Cdc13, Yku and telomerase, mainly, prevent telomere uncapping, thus providing telomere stability and avoiding degradation and death by senescence. Here, we report that in the absence of Mrc1, a component of the replication forks, telomeres of cdc13 or yku70 mutants exhibited increased degradation, while telomerase-negative cells displayed accelerated senescence. Moreover, deletion of MRC1 increased the single-strandedness of the telomeres in cdc13-1 and yku70Δ mutant strains. An mrc1 deletion strain also exhibited slight but stable telomere shortening compared to a wild-type strain. Loss of Mrc1’s checkpoint function alone did not provoke synthetic growth defects in combination with the cdc13-1 mutation. Combinations between the cdc13-1 mutation and deletion of either TOF1 or PSY2, coding for proteins physically interacting with Mrc1, also resulted in a synthetic growth defect. Thus, the present data suggest that non-essential components of the DNA replication machinery, such as Mrc1 and Tof1, may have a role in telomere stability in addition to their role in fork progression.
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Acknowledgments
We thank Stephen Elledge, Leland Hartwell, Dan Gottschling and Wei Xiao for the gifts of strains and plasmids. This work was supported by grants from the “Association pour la Recherche contre le Cancer”, the INCa (“Institut National du Cancer”; EPIPRO program to Saadi Kochblin and Eric Gilson) and the “Comité Départemental de la Savoie de la Ligue Nationale contre le Cancer”.
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Grandin, N., Charbonneau, M. Mrc1, a non-essential DNA replication protein, is required for telomere end protection following loss of capping by Cdc13, Yku or telomerase. Mol Genet Genomics 277, 685–699 (2007). https://doi.org/10.1007/s00438-007-0218-0
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DOI: https://doi.org/10.1007/s00438-007-0218-0