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Altered dosage of the Saccharomyces cere ... ds to aneuploidy and polyploidy
Altered dosage of the Saccharomyces cerevisiae spindle pole body duplication gene, NDC1, leads to aneuploidy and polyploidy.
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Saccharomyces cerevisiae cells are exquisitely sensitive to altered dosage of the spindle pole body duplication gene, NDC1. We show that the NDC1 locus is haploinsufficient because diploid yeast cells cannot survive with a single chromosomal copy of the NDC1 gene. Diploid cells with a single copy of NDC1 can survive by gaining an extra copy of the NDC1-containing chromosome. NDC1 haploinsufficiency is a dominant loss-of-function phenotype that leads to aneuploidy. Furthermore, we report that overexpression of NDC1 leads to spindle pole body duplication defects indistinguishable from those observed in ndc1-1 mutant cells. Cells overexpressing NDC1 arrest with monopolar spindles and exhibit increase-in-ploidy phenotypes. Thus, both increased and decreased NDC1 dosage can lead to aneuploidy. The striking sensitivity of yeast cells to changes in NDC1 gene dosage suggests a model for the behavior of some tumor suppressor genes and oncogenes in which loss-of-function mutations and overexpression, respectively, lead to increased genetic instability.
Chial HJ, Giddings TH, Siewert EA, Hoyt MA, Winey M
Proceedings of the National Academy of Sciences of the United States of America
1999-08-31 00:00
96
18
10200-5
Aneuploidy,Fungal Proteins,Gene Dosage,Genotype,Mitotic Spindle Apparatus,Nuclear Proteins,Phenotype,Polyploidy,Saccharomyces cerevisiae,Saccharomyces cerevisiae Proteins,Fungal Proteins,NDC1 protein, S cerevisiae,Nuclear Proteins,Saccharomyces cerevisiae Proteins
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA
Proc. Natl. Acad. Sci. U.S.A.
NIGMS GM-07135
0027-8424
1232
True
10468586
