Altered dosage of the Saccharomyces cerevisiae spindle pole body duplication gene, NDC1, leads to aneuploidy and polyploidy

H. J. Chial, T. H. Giddings, E. A. Siewert, M. A. Hoyt, Mark Winey

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10200-10205
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number18
DOIs
StatePublished - Aug 31 1999
Externally publishedYes

Fingerprint

Spindle Pole Bodies
Polyploidy
Gene Duplication
Aneuploidy
Saccharomyces cerevisiae
Diploidy
Yeasts
Phenotype
Haploinsufficiency
Gene Dosage
Ploidies
Tumor Suppressor Genes
Oncogenes
Chromosomes
Mutation
Genes

ASJC Scopus subject areas

  • General

Cite this

Altered dosage of the Saccharomyces cerevisiae spindle pole body duplication gene, NDC1, leads to aneuploidy and polyploidy. / Chial, H. J.; Giddings, T. H.; Siewert, E. A.; Hoyt, M. A.; Winey, Mark.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 18, 31.08.1999, p. 10200-10205.

Research output: Contribution to journalArticle

@article{ca580360cdb848d183b603f6c1b3efb0,
title = "Altered dosage of the Saccharomyces cerevisiae spindle pole body duplication gene, NDC1, leads to aneuploidy and polyploidy",
abstract = "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.",
author = "Chial, {H. J.} and Giddings, {T. H.} and Siewert, {E. A.} and Hoyt, {M. A.} and Mark Winey",
year = "1999",
month = "8",
day = "31",
doi = "10.1073/pnas.96.18.10200",
language = "English (US)",
volume = "96",
pages = "10200--10205",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "18",

}

TY - JOUR

T1 - Altered dosage of the Saccharomyces cerevisiae spindle pole body duplication gene, NDC1, leads to aneuploidy and polyploidy

AU - Chial, H. J.

AU - Giddings, T. H.

AU - Siewert, E. A.

AU - Hoyt, M. A.

AU - Winey, Mark

PY - 1999/8/31

Y1 - 1999/8/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033621063&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033621063&partnerID=8YFLogxK

U2 - 10.1073/pnas.96.18.10200

DO - 10.1073/pnas.96.18.10200

M3 - Article

C2 - 10468586

AN - SCOPUS:0033621063

VL - 96

SP - 10200

EP - 10205

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 18

ER -