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Linear chromosome maintenance in the absence of essential telomere-capping proteins

Nature Cell Biology volume 8, pages 734–740 (2006)Cite this article

Abstract

Telomeres were defined by their ability to cap chromosome ends1,2. Proteins with high affinity for the structure at chromosome ends, binding the G-rich, 3′ single-stranded overhang at telomeres include Pot1 in humans and fission yeast, TEBP in Oxytricha nova and Cdc13 in budding yeast3,4,5. Cdc13 is considered essential for telomere capping because budding yeast that lack Cdc13 rapidly accumulate excessive single-stranded DNA (ssDNA) at telomeres, arrest cell division and die6,7,8. Cdc13 has a separate, critical role in telomerase recruitment to telomeres9,10. Here, we show that neither Cdc13 nor its partner Stn1 are necessary for telomere capping if nuclease activities that are active at uncapped telomeres are attenuated. Recombination-dependent and -independent mechanisms permit maintenance of chromosomes without Cdc13. Our results indicate that the structure of the eukaryotic telomere cap is remarkably flexible and that changes in the DNA damage response allow alternative strategies for telomere capping to evolve.

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Figure 1: Growth of cdc13-1 mutants at 36 °C.
Figure 2: Temperature-resistant cdc13-1 strains show altered telomeric DNA patterns.
Figure 3: Temperature-resistant cdc13-1 cells divide in the absence of Rad52-dependent recombination.
Figure 4: CDC13 is not essential for chromosome maintenance.
Figure 5: Telomeric DNA in the absence of Cdc13 and Stn1.

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Acknowledgements

We thank all members of our lab for input, particularly S. Foster for providing a CDC15 probe, and T. Kirkwood, L. Maringele, C. Nugent, G. Sareztki, R. Wellinger and T. von Zglinicki for comments on the manuscript. We are grateful to C. Nugent and R. Wellinger for communicating data before publication. This work was supported by the Wellcome Trust (Grant numbers 054371and 075294).

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Authors and Affiliations

  1. Institute for Ageing and Health, Henry Wellcome Laboratory for Biogerontology Research, University of Newcastle, Newcastle upon Tyne, NE4 6BE, UK

    Mikhajlo K. Zubko & David Lydall

  2. Institute for Cell and Molecular Biosciences, Henry Wellcome Laboratory for Biogerontology Research, University of Newcastle, Newcastle upon Tyne, NE4 6BE, UK

    David Lydall

  3. Centre for Integrated Systems Biology of Ageing and Nutrition, Henry Wellcome Laboratory for Biogerontology Research, University of Newcastle, Newcastle upon Tyne, NE4 6BE, UK

    David Lydall

Authors
  1. Mikhajlo K. Zubko
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  2. David Lydall
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Contributions

M.Z. performed all experiments and made the initial observation that cdc13-1 mutants could grow at 36 °C. M.Z. and D.L. designed subsequent experiments. D.L. wrote the bulk of the paper.

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Correspondence to David Lydall.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Figures S1, S2, S3, S4, Supplementary Tables S1, S2, S3 and Supplementary Data (PDF 877 kb)

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Zubko, M., Lydall, D. Linear chromosome maintenance in the absence of essential telomere-capping proteins. Nat Cell Biol 8, 734–740 (2006). https://doi.org/10.1038/ncb1428

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