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.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: Tessie M
authors.initials: TM
authors.lastname: Ng
authors.forename: Tineke L
authors.initials: TL
authors.lastname: Lenstra
authors.forename: Nicole
authors.initials: N
authors.lastname: Duggan
authors.forename: Shuangying
authors.initials: S
authors.lastname: Jiang
authors.forename: Steven
authors.initials: S
authors.lastname: Ceto
authors.forename: Frank C P
authors.initials: FC
authors.lastname: Holstege
authors.forename: Junbiao
authors.initials: J
authors.lastname: Dai
authors.forename: Jef D
authors.initials: JD
authors.lastname: Boeke
authors.forename: Sue
authors.initials: S
authors.lastname: Biggins
mesh_terms: D001665:Binding Sites; D002503:Centromere / Q000235:genetics / Q000378:metabolism; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics* / Q000502:physiology; D015825:Chromosomes, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage; D005800:Genes, Fungal; D006657:Histones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C092746:CSE4 protein, S cerevisiae; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C482640:Sgo1 protein, S cerevisiae
keywords: biorientation; chromosomal passenger complex (CPC); chromosome segregation; histones; kinetochore
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