Article
Paclitaxel-induced microtubule stabilization causes mitotic block and apoptotic-like cell death in a paclitaxel-sensitive strain of Saccharomyces cerevisiae
Yeast
(2005)
Abstract
Wild-type Saccharomyces cerevisiae tubulin does not bind the anti-mitotic microtubule stabilizing
agent paclitaxel. Previously, we introduced mutations into the S. cerevisiae gene for β-tubulin that
imparted paclitaxel binding to the protein, but the mutant strain was not sensitive to paclitaxel and
other microtubule-stabilizing agents, due to the multiple ABC transporters in the membranes of
budding yeast. Here, we introduced the mutated β-tubulin gene into a S. cerevisiae strain with
diminished transporter activity and developed the first paclitaxel-sensitive budding yeast strain. In
the presence of paclitaxel, cytoplasmic microtubules were stable to cold depolymerization.
Paclitaxel-treated cells showed evidence of a mitotic block, with an increase in large-budded cells
and cells with a 2N DNA content and DNA fragmentation, identified by FACS analysis and the
TUNEL assay. In the presence of paclitaxel, the number of dead cells in cultures increased threefold
and cells containing reactive oxygen species were present. We conclude that paclitaxel blocks
mitosis in this strain, leading to an apoptotic-like cell death. This strain will also be useful in
further studies of the effect of microtubule dynamics on various cellular processes in S. cerevisiae.
Keywords
- paclitaxel,
- tubulin,
- microtubules,
- yeast,
- apoptosis
Disciplines
Publication Date
September, 2005
DOI
10.1002/yea.1284
Publisher Statement
Copyright © 2005 John Wiley & Sons, Inc
Citation Information
Travis B. Foland, William L. Dentler, Kathy A. Suprenant, Mohan L. Gupta, et al.. "Paclitaxel-induced microtubule stabilization causes mitotic block and apoptotic-like cell death in a paclitaxel-sensitive strain of Saccharomyces cerevisiae" Yeast Vol. 22 Iss. 12 (2005) p. 971 - 978 Available at: http://works.bepress.com/mohan-gupta/7/