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 - Nov 11 2013

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    ASJC Scopus subject areas

    • Genetics

    Cite this

    Ng, T. M., Lenstra, T. L., Duggan, N., Jiang, S., Ceto, S., Holstege, F. C. P., Dai, J., Boeke, J. D., & 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