Histone H2A is required for normal centromere function in Saccharomyces cerevisiae

Pinto, Inês Mendes; Winston, Fred

doi:10.1093/emboj/19.7.1598

Cited by 60 publications

(67 citation statements)

References 65 publications

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“…Although H3 was also reported to localize to centromeres in budding yeast (Lochmann and Ivanov 2012), the region of DNA analyzed was large enough to contain two nucleosomes so the H3 detected may be in the neighboring nucleosome rather than the centromeric nucleosome. Consistent with this, depletion of H3 in budding yeast has little effect on kinetochore function compared to H4 depletion or H2A mutations that lead to defects in kinetochore-microtubule attachments (Pinto and Winston 2000;Bouck and Bloom 2007;Verdaasdonk et al 2012). Together, these data suggest that H3 does not reside at the point centromere, although it is important for accurate segregation through its role in recruiting Sgo1 to the pericentromere and facilitating inner kinetochore function (Luo et al 2010;Verdaasdonk et al 2012).…”

Section: Centromeric Chromatinmentioning

confidence: 61%

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

2013

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The propagation of all organisms depends on the accurate and orderly segregation of chromosomes in mitosis and meiosis. Budding yeast has long served as an outstanding model organism to identify the components and underlying mechanisms that regulate chromosome segregation. This review focuses on the kinetochore, the macromolecular protein complex that assembles on centromeric chromatin and maintains persistent load-bearing attachments to the dynamic tips of spindle microtubules. The kinetochore also serves as a regulatory hub for the spindle checkpoint, ensuring that cell cycle progression is coupled to the achievement of proper microtubule-kinetochore attachments. Progress in understanding the composition and overall architecture of the kinetochore, as well as its properties in making and regulating microtubule attachments and the spindle checkpoint, is discussed. TABLE OF CONTENTS Abstract 817Introduction 818

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Section: Centromeric Chromatinmentioning

confidence: 61%

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

2013

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“…In budding yeast, the bulk of DNA is wrapped around a canonical histone octamer composed of two molecules of each of four histones, H2A, H2B, H3, and H4. Cse4 has been shown to copurify with H2A, H2B, and H4, as well as exhibit genetic interactions with H2A and H4 (10,44,45), suggesting that centromeric nucleosomes are structurally similar to canonical nucleosomes. However, a recent study suggests that Cse4 and canonical H4 associate with the nonhistone protein Scm3 instead of H2A and H2B to form a novel hexameric nucleosomal core structure at the CEN (20).…”

Section: Discussionmentioning

confidence: 99%

Centromere identity is specified by a single centromeric nucleosome in budding yeast

Furuyama

Biggins

2007

Proc. Natl. Acad. Sci. U.S.A.

239

216

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Chromosome segregation ensures that DNA is equally divided between daughter cells during each round of cell division. The centromere (CEN) is the specific locus on each chromosome that directs formation of the kinetochore, the multiprotein complex that interacts with the spindle microtubules to promote proper chromosomal alignment and segregation during mitosis. CENs are organized into a specialized chromatin structure due to the incorporation of an essential CEN-specific histone H3 variant ( CenH3 ͉ chromatin ͉ kinetochore C hromosome segregation is directed by the multiprotein kinetochore (KT) complex that assembles on centromeres (CENs) and interacts with the spindle apparatus to control chromosome movement during cell division (for reviews, see refs. 1 and 2). Although KT function is conserved, phylogenetic analysis of centromeric DNA reveals no common sequence element that would identify a CEN across species. Like all other parts of the genome, the DNA of CENs is organized into chromatin, a higher order structure in which DNA is wrapped around histones to generate nucleosomes. Typical octameric nucleosomes contain two molecules of each of four histones, H2A, H2B, H3, and H4, whereas centromeric nucleosomes are structurally distinct, containing an evolutionarily conserved CEN-specific histone H3 variant (CenH3) in place of canonical H3 (for review, see ref.3). The conservation of CenH3 across eukaryotes and its strict CEN localization in all species suggest that it is the epigenetic CEN identifier. Consistent with this finding, overexpression of the Drosophila CenH3 leads to its localization in euchromatin and the formation of ectopic KTs, resulting in subsequent defects in genomic stability (4).Despite the requirement for CenH3 in CEN specification, it is unclear how CenH3 nucleosomes structurally organize centromeric DNA to promote KT formation. In humans, CenH3 associates with centromeric ␣ satellite repeats (5), resulting in megabase expanses of centromeric nucleosomes. These centromeric nucleosomes drive the assembly of the KT structure that interacts with multiple microtubules. However, the number of CenH3 nucleosomes far exceeds the number of microtubules associated with a CEN, making the minimal number and arrangement of CenH3 nucleosomes necessary to assemble a single functional KT unclear. In flies and humans, blocks of CenH3 nucleosomes are interspersed with blocks of H3 nucleosomes (6), suggesting that higher order folding of the centromeric

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“…The first cluster (K13, K15, and K36) is partially located in the NH 2 -terminal tail domain that is projecting out from the nucleosome through a minor groove in the DNA duplex. These sites of modification are also in a region of the protein shown to be required for normal centromere function in yeast [Pinto and Winston, 2000]. The second cluster (K74, K75, and K77) is located in the L2 loop which is another contact point between H2A and DNA.…”

Section: Identification Of Sites Of Histone Modification By Mass Specmentioning

confidence: 98%

Application of mass spectrometry to the identification and quantification of histone post‐translational modifications

Freitas

Sklenar

Parthun

2004

J of Cellular Biochemistry

130

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The core histories are the primary protein component of chromatin, which is responsible for the packaging of eukaryotic DNA. The NH 2 -terminal tail domains of the core histones are the sites of numerous post-translational modifications that have been shown to play an important role in the regulation of chromatin structure. In this study, we discuss the recent application of modern analytical techniques to the study of histone modifications. Through the use of mass spectrometry, a large number of new sites of histone modification have been identified, many of which reside outside of the NH 2 -terminal tail domains. In addition, techniques have been developed that allow mass spectrometry to be effective for the quantitation of histone post-translational modifications. Hence, the use of mass spectrometry promises to dramatically alter our view of histone post-translational modifications.

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Histone H2A is required for normal centromere function in Saccharomyces cerevisiae

Cited by 60 publications

References 65 publications

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

Centromere identity is specified by a single centromeric nucleosome in budding yeast

Application of mass spectrometry to the identification and quantification of histone post‐translational modifications

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