Novel Response to Microtubule Perturbation in Meiosis

Abstract

During the mitotic cell cycle, microtubule depolymerization leads to a cell cycle arrest in metaphase, due to activation of the spindle checkpoint. Here, we show that under microtubule-destabilizing conditions, such as low temperature or the presence of the spindle-depolymerizing drug benomyl, meiotic budding yeast cells arrest in G₁ or G₂, instead of metaphase. Cells arrest in G₁ if microtubule perturbation occurs as they enter the meiotic cell cycle and in G₂ if cells are already undergoing premeiotic S phase. Concomitantly, cells down-regulate genes required for cell cycle progression, meiotic differentiation, and spore formation in a highly coordinated manner. Decreased expression of these genes is likely to be responsible for halting both cell cycle progression and meiotic development. Our results point towards the existence of a novel surveillance mechanism of microtubule integrity that may be particularly important during specialized cell cycles when coordination of cell cycle progression with a developmental program is necessary.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/.

ACKNOWLEDGMENTS

We are grateful to N. Kleckner and F. Solomon for reagents and advice and to S. Biggins for sharing unpublished results. We thank F. Solomon and members of the Amon lab for their critical reading of the manuscript. We thank L. Hermida for administration of the GermOnline database.

P.D. and G.W. are supported by the Department of Clinical and Biological Sciences and the Biozentrum, respectively. M.C. and C.N.-W. are supported by the Swiss Institute of Bioinformatics. This research was supported by a National Institutes of Health grant (GM62207) to A.A. A.A. is an Investigator of the Howard Hughes Medical Institute.