期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：18
页码：10200-10205
DOI：10.1073/pnas.96.18.10200
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
