Current Genetics

, Volume 50, Issue 5, pp 281–294 | Cite as

Chromosome segregation in fission yeast with mutations in the tubulin folding cofactor D

  • Olga S. Fedyanina
  • Pavel V. Mardanov
  • Ekaterina M. Tokareva
  • J. Richard McIntosh
  • Ekaterina L. Grishchuk
Research Article
First Online:
Received:
Revised:
Accepted:

Abstract

Faithful chromosome segregation requires the combined activities of the microtubule-based mitotic spindle and the multiple proteins that form mitotic kinetochores. Here, we show that the fission yeast mitotic mutant, tsm1-512, is an allele of the tubulin folding chaperone, cofactor D. Chromosome segregation in this and in an additional cofactor D mutant depends on growth conditions that are monitored specifically by the mitotic checkpoint proteins Mad1, 2, 3 and Bub3. The temperature-sensitive mutants we have used disrupt the function of cofactor D to different extents, but both strains form a mitotic spindle in which the poles separate in anaphase. However, chromosome segregation is often unequal, apparently due to a defect in kinetochore–microtubule interactions. Mutations in cofactor D render cells particularly sensitive to the expression levels of a CENP-B-like protein, Abp1p, which works as an allele-specific, high-copy suppressor of cofactor D. This and other genetic interactions between cofactor D mutants and specific kinetochore and spindle components suggest their critical role in establishing the normal kinetochore–microtubule interface.

Keywords

CENP-B Chromosome segregation Fission yeast Kinetochore Microtubule Tubulin-folding cofactor 
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Notes

Acknowledgments

We are grateful to M. Baum and L. Clarke (University of CA, Santa Barbara), T. Toda (ICRF, London, UK), T. E. Patterson and S. Sazer (Baylor College of Medicine, Houston, TX), K. Hardwick (University of Edinburgh, UK), M. Yanagida (Kyoto University, Japan), K. Gould (Vanderbilt University, Nashville, TN) and I. Hagan (University of Leicester, UK) for providing strains, plasmids, minichromosome and other reagents used in this study; to J. Kohli (University of Bern, Switzerland) for a generous gift of a Nikon microscope equipped with micromanipulator for tetrad analysis; to R. R. West (University of Colorado, Boulder, USA) for critical reading of the manuscript; F. I. Ataullakhanov (National Research Center for Hematology, Moscow, Russia) for helpful discussions and suggestions. A. Book helped with determining viability of the synchronized mutant strains; L. Tran, A. Tikunov and A. Pivovarova carried out some of the genetic crosses. This work was supported in part by the grant from Russian Foundation for Basic Research, project no. 00-04-48449 to EG and by GM33787 from the NIH to JRM.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Olga S. Fedyanina
    • 1
  • Pavel V. Mardanov
    • 2
  • Ekaterina M. Tokareva
    • 1
  • J. Richard McIntosh
    • 3
  • Ekaterina L. Grishchuk
    • 3
    • 4
  1. 1.National Research Center for HematologyMoscowRussia
  2. 2.Institute of Gene BiologyMoscowRussia
  3. 3.M.C.D. Biology DepartmentUniversity of ColoradoBoulderUSA
  4. 4.Institute of General Pathology and PathophysiologyMoscowRussia

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