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Originally published as MBC in Press, 10.1091/mbc.E04-02-0094 on May 14, 2004

Vol. 15, Issue 8, 3796-3810, August 2004

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Functional Characterization of Dma1 and Dma2, the Budding Yeast Homologues of Schizosaccharomyces pombe Dma1 and Human Chfr

Roberta Fraschini, Denis Bilotta, Giovanna Lucchini, and Simonetta Piatti *

Dipartimento di Biotecnologie e Bioscienze, Piazza della Scienza 2, 20126 Milan, Italy

Submitted February 4, 2004; Accepted May 5, 2004
Monitoring Editor: Tim Stearns

Proper transmission of genetic information requires correct assembly and positioning of the mitotic spindle, responsible for driving each set of sister chromatids to the two daughter cells, followed by cytokinesis. In case of altered spindle orientation, the spindle position checkpoint inhibits Tem1-dependent activation of the mitotic exit network (MEN), thus delaying mitotic exit and cytokinesis until errors are corrected. We report a functional analysis of two previously uncharacterized budding yeast proteins, Dma1 and Dma2, 58% identical to each other and homologous to human Chfr and Schizosaccharomyces pombe Dma1, both of which have been previously implicated in mitotic checkpoints. We show that Dma1 and Dma2 are involved in proper spindle positioning, likely regulating septin ring deposition at the bud neck. DMA2 overexpression causes defects in septin ring disassembly at the end of mitosis and in cytokinesis. The latter defects can be rescued by either eliminating the spindle position checkpoint protein Bub2 or overproducing its target, Tem1, both leading to MEN hyperactivation. In addition, dma1{Delta} dma2{Delta} cells fail to activate the spindle position checkpoint in response to the lack of dynein, whereas ectopic expression of DMA2 prevents unscheduled mitotic exit of spindle checkpoint mutants treated with microtubule-depolymerizing drugs. Although their primary functions remain to be defined, our data suggest that Dma1 and Dma2 might be required to ensure timely MEN activation in telophase.


Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E04-02-0094. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E04-02-0094.

Online version of this article contains supporting material. Online version is available at www.molbiolcell.org.

* Corresponding author. E-mail address: simonetta.piatti{at}unimib.it.




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