Kinetochore function and chromosome segregation rely on critical residues in histones H3 and H4 in budding yeast

Tessie M. Ng, Tineke L. Lenstra, Nicole Duggan, Shuangying Jiang, Steven Ceto, Frank C P Holstege, Junbiao Dai, Jef D. Boeke, Sue Biggins

Research output: Contribution to journalArticle

Abstract

Accurate chromosome segregation requires that sister kinetochores biorient and attach to microtubules from opposite poles. Kinetochore biorientation relies on the underlying centromeric chromatin, which provides a platform to assemble the kinetochore and to recruit the regulatory factors that ensure the high fidelity of this process. To identify the centromeric chromatin determinants that contribute to chromosome segregation, we performed two complementary unbiased genetic screens using a library of budding yeast mutants in every residue of histone H3 and H4. In one screen, we identified mutants that lead to increased loss of a nonessential chromosome. In the second screen, we isolated mutants whose viability depends on a key regulator of biorientation, the Aurora B protein kinase. Nine mutants were common to both screens and exhibited kinetochore biorientation defects. Four of the mutants map near the unstructured nucleosome entry site, and their genetic interaction with reduced IPL1 can be suppressed by increasing the dosage of SGO1, a key regulator of biorientation. In addition, the composition of purified kinetochores was altered in six of the mutants. Together, this work identifies previously unknown histone residues involved in chromosome segregation and lays the foundation for future studies on the role of the underlying chromatin structure in chromosome segregation.

Original languageEnglish (US)
Pages (from-to)795-807
Number of pages13
JournalGenetics
Volume195
Issue number3
DOIs
StatePublished - 2013

Fingerprint

Kinetochores
Chromosome Segregation
Saccharomycetales
Histones
Chromatin
Aurora Kinase B
Nucleosomes
Microtubules
Libraries
Chromosomes

ASJC Scopus subject areas

  • Genetics

Cite this

Ng, T. M., Lenstra, T. L., Duggan, N., Jiang, S., Ceto, S., Holstege, F. C. P., ... Biggins, S. (2013). Kinetochore function and chromosome segregation rely on critical residues in histones H3 and H4 in budding yeast. Genetics, 195(3), 795-807. https://doi.org/10.1534/genetics.113.152082

Kinetochore function and chromosome segregation rely on critical residues in histones H3 and H4 in budding yeast. / Ng, Tessie M.; Lenstra, Tineke L.; Duggan, Nicole; Jiang, Shuangying; Ceto, Steven; Holstege, Frank C P; Dai, Junbiao; Boeke, Jef D.; Biggins, Sue.

In: Genetics, Vol. 195, No. 3, 2013, p. 795-807.

Research output: Contribution to journalArticle

Ng, TM, Lenstra, TL, Duggan, N, Jiang, S, Ceto, S, Holstege, FCP, Dai, J, Boeke, JD & Biggins, S 2013, 'Kinetochore function and chromosome segregation rely on critical residues in histones H3 and H4 in budding yeast', Genetics, vol. 195, no. 3, pp. 795-807. https://doi.org/10.1534/genetics.113.152082
Ng, Tessie M. ; Lenstra, Tineke L. ; Duggan, Nicole ; Jiang, Shuangying ; Ceto, Steven ; Holstege, Frank C P ; Dai, Junbiao ; Boeke, Jef D. ; Biggins, Sue. / Kinetochore function and chromosome segregation rely on critical residues in histones H3 and H4 in budding yeast. In: Genetics. 2013 ; Vol. 195, No. 3. pp. 795-807.
@article{f6cd55c8b8e643e48ff6d0a8db014474,
title = "Kinetochore function and chromosome segregation rely on critical residues in histones H3 and H4 in budding yeast",
abstract = "Accurate chromosome segregation requires that sister kinetochores biorient and attach to microtubules from opposite poles. Kinetochore biorientation relies on the underlying centromeric chromatin, which provides a platform to assemble the kinetochore and to recruit the regulatory factors that ensure the high fidelity of this process. To identify the centromeric chromatin determinants that contribute to chromosome segregation, we performed two complementary unbiased genetic screens using a library of budding yeast mutants in every residue of histone H3 and H4. In one screen, we identified mutants that lead to increased loss of a nonessential chromosome. In the second screen, we isolated mutants whose viability depends on a key regulator of biorientation, the Aurora B protein kinase. Nine mutants were common to both screens and exhibited kinetochore biorientation defects. Four of the mutants map near the unstructured nucleosome entry site, and their genetic interaction with reduced IPL1 can be suppressed by increasing the dosage of SGO1, a key regulator of biorientation. In addition, the composition of purified kinetochores was altered in six of the mutants. Together, this work identifies previously unknown histone residues involved in chromosome segregation and lays the foundation for future studies on the role of the underlying chromatin structure in chromosome segregation.",
author = "Ng, {Tessie M.} and Lenstra, {Tineke L.} and Nicole Duggan and Shuangying Jiang and Steven Ceto and Holstege, {Frank C P} and Junbiao Dai and Boeke, {Jef D.} and Sue Biggins",
year = "2013",
doi = "10.1534/genetics.113.152082",
language = "English (US)",
volume = "195",
pages = "795--807",
journal = "Genetics",
issn = "0016-6731",
publisher = "Genetics Society of America",
number = "3",

}

TY - JOUR

T1 - Kinetochore function and chromosome segregation rely on critical residues in histones H3 and H4 in budding yeast

AU - Ng, Tessie M.

AU - Lenstra, Tineke L.

AU - Duggan, Nicole

AU - Jiang, Shuangying

AU - Ceto, Steven

AU - Holstege, Frank C P

AU - Dai, Junbiao

AU - Boeke, Jef D.

AU - Biggins, Sue

PY - 2013

Y1 - 2013

N2 - Accurate chromosome segregation requires that sister kinetochores biorient and attach to microtubules from opposite poles. Kinetochore biorientation relies on the underlying centromeric chromatin, which provides a platform to assemble the kinetochore and to recruit the regulatory factors that ensure the high fidelity of this process. To identify the centromeric chromatin determinants that contribute to chromosome segregation, we performed two complementary unbiased genetic screens using a library of budding yeast mutants in every residue of histone H3 and H4. In one screen, we identified mutants that lead to increased loss of a nonessential chromosome. In the second screen, we isolated mutants whose viability depends on a key regulator of biorientation, the Aurora B protein kinase. Nine mutants were common to both screens and exhibited kinetochore biorientation defects. Four of the mutants map near the unstructured nucleosome entry site, and their genetic interaction with reduced IPL1 can be suppressed by increasing the dosage of SGO1, a key regulator of biorientation. In addition, the composition of purified kinetochores was altered in six of the mutants. Together, this work identifies previously unknown histone residues involved in chromosome segregation and lays the foundation for future studies on the role of the underlying chromatin structure in chromosome segregation.

AB - Accurate chromosome segregation requires that sister kinetochores biorient and attach to microtubules from opposite poles. Kinetochore biorientation relies on the underlying centromeric chromatin, which provides a platform to assemble the kinetochore and to recruit the regulatory factors that ensure the high fidelity of this process. To identify the centromeric chromatin determinants that contribute to chromosome segregation, we performed two complementary unbiased genetic screens using a library of budding yeast mutants in every residue of histone H3 and H4. In one screen, we identified mutants that lead to increased loss of a nonessential chromosome. In the second screen, we isolated mutants whose viability depends on a key regulator of biorientation, the Aurora B protein kinase. Nine mutants were common to both screens and exhibited kinetochore biorientation defects. Four of the mutants map near the unstructured nucleosome entry site, and their genetic interaction with reduced IPL1 can be suppressed by increasing the dosage of SGO1, a key regulator of biorientation. In addition, the composition of purified kinetochores was altered in six of the mutants. Together, this work identifies previously unknown histone residues involved in chromosome segregation and lays the foundation for future studies on the role of the underlying chromatin structure in chromosome segregation.

UR - http://www.scopus.com/inward/record.url?scp=84887075638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887075638&partnerID=8YFLogxK

U2 - 10.1534/genetics.113.152082

DO - 10.1534/genetics.113.152082

M3 - Article

C2 - 24037263

AN - SCOPUS:84887075638

VL - 195

SP - 795

EP - 807

JO - Genetics

JF - Genetics

SN - 0016-6731

IS - 3

ER -