Psh1 Is an E3 Ubiquitin Ligase that Targets the Centromeric Histone Variant Cse4

Hewawasam, Geetha S.; Shivaraju, Manjunatha; Mattingly, Mark; Venkatesh, Swaminathan; Martin-Brown, Skylar; Florens, Laurence; Workman, Jerry L.; Gerton, Jennifer L.

doi:10.1016/j.molcel.2010.10.014

Cited by 163 publications

(285 citation statements)

References 23 publications

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“…In principle, two Cse4 hemisomes may jointly constrain one positive writhe, which will be converted to one negative writhe if only one H3 nucleosome substitutes for their absence. In light of the stringent regulation of Cse4 in the nucleus by protein turnover (34)(35)(36), its absence from the majority of STB plasmids in their multicopy state (24), and its quantitative occupancy of low-copy plasmids, we favor a functional stoichiometry of one Cse4 nucleosome per STB.…”

Section: Discussionmentioning

confidence: 98%

Histone H3-variant Cse4-induced positive DNA supercoiling in the yeast plasmid has implications for a plasmid origin of a chromosome centromere

Huang

Chang

Cui

et al. 2011

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

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The Saccharomyces cerevisiae 2-μm plasmid is a multicopy selfish genome that resides in the nucleus. The genetic organization of the plasmid is optimized for stable, high-copy propagation in hostcell populations. The plasmid's partitioning system poaches host factors, including the centromere-specific histone H3-variant Cse4 and the cohesin complex, enabling replicated plasmid copies to segregate equally in a chromosome-coupled fashion. We have characterized the in vivo chromatin topology of the plasmid partitioning locus STB in its Cse4-associated and Cse4-nonassociated states. We find that the occupancy of Cse4 at STB induces positive DNA supercoiling, with a linking difference (ΔLk) contribution estimated between +1 and +2 units. One plausible explanation for this contrary topology is the presence of a specialized Cse4-containing nucleosome with a right-handed DNA writhe at a functional STB, contrasted by a standard histone H3-containing nucleosome with a left-handed DNA writhe at a nonfunctional STB. The similarities between STB and centromere in their nucleosome signature and DNA topology would be consistent with the potential origin of the unusual point centromere of budding yeast chromosomes from the partitioning locus of an ancestral plasmid.CEN evolution | nucleosome topology | reversome T he 2-μm plasmid of Saccharomyces cerevisiae resides in the nucleus at 40 to 60 copies per cell, and propagates itself with nearly the same stability as chromosomes (1, 2). The plasmid is a benign selfish DNA element that seems to provide no advantage to its host, but poses, at its normal copy number, no serious disadvantage either. In haploid cells the plasmid is organized into a cluster of three to five foci, and segregates as a cluster (3). This effective reduction in copy number necessitates an active partitioning system, comprised of two plasmid-coded proteins, Rep1 and Rep2, and a cis-acting partitioning locus STB, to ensure equal or nearly equal plasmid segregation. A decline in plasmid copy number because of rare missegregation events is corrected via DNA amplification triggered by the Flp sitespecific recombination system harbored by the plasmid (4, 5). Positive and negative regulatory circuits implemented through the plasmid-coded Raf1 protein and the Rep proteins ensure quick amplification response without the danger of runaway increase in copy number (6-8).The Rep-STB system channels several host factors involved in chromosome segregation toward the execution of plasmid segregation. These factors include the mitotic spindle, the spindleassociated motor Kip1, the RSC2 chromatin-remodeling complex, the centromere-specific histone H3-variant Cse4 (CenH3), and the yeast cohesin complex (9-15). The de novo assembly of the plasmid-partitioning complex at STB during the G1-S window of each cell cycle (9,12,14,16) is reminiscent of the assembly of the kinetochore complex at centromeres. However, kinetochore components have not been detected at STB by ChIP (13).The assembly of the plasmid-partitioning complex culmin...

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Section: Discussionmentioning

confidence: 98%

Histone H3-variant Cse4-induced positive DNA supercoiling in the yeast plasmid has implications for a plasmid origin of a chromosome centromere

Huang

Chang

Cui

et al. 2011

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

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“…[8][9][10] scm3-1 cells were suppressed by high gene dosage of CSE4, which is consistent with the functional interplay of both gene products. [8][9][10] Moreover, high gene dosage of the PSH1 gene, coding for an E3 ubiquitin ligase that ubiquitinates Cse4 under overexpression conditions, 18,19 increased the growth defect of scm3-1 cells. This result is in agreement with the proposed competition of Psh1 and Scm3 for Cse4 binding.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

“…This phenotype is consistent with a protecting function of Scm3 toward Psh1 and provides in vivo evidence for the counteracting role of Scm3 and Psh1. 18,19 that leads to a truncation of 13 codons (Fig. S2A).…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

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The CENP-A chaperone Scm3 becomes enriched at kinetochores in anaphase independently of CENP-A incorporation

et al. 2011

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“…In S. cerevisiae, the E3 ubiquitin ligase Psh1 has been shown to target CENP-A Cse4 for degradation (Hewawasam et al 2010;Ranjitkar et al 2010). Psh1 localizes to centromeres, but is thought to act on noncentromeric CENP-A Cse4 .…”

Section: Additional Factors Involved In Cenp-a Assemblymentioning

confidence: 99%

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Westhorpe

Straight

2014

Cold Spring Harb Perspect Biol

142

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A fundamental challenge for the survival of all organisms is maintaining the integrity of the genome in all cells. Cells must therefore segregate their replicated genome equally during each cell division. Eukaryotic organisms package their genome into a number of physically distinct chromosomes, which replicate during S phase and condense during prophase of mitosis to form paired sister chromatids. During mitosis, cells form a physical connection between each sister chromatid and microtubules of the mitotic spindle, which segregate one copy of each chromatid to each new daughter cell. The centromere is the DNA locus on each chromosome that creates the site of this connection. In this review, we present a brief history of centromere research and discuss our current knowledge of centromere establishment, maintenance, composition, structure, and function in mitosis.

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Psh1 Is an E3 Ubiquitin Ligase that Targets the Centromeric Histone Variant Cse4

Cited by 163 publications

References 23 publications

Histone H3-variant Cse4-induced positive DNA supercoiling in the yeast plasmid has implications for a plasmid origin of a chromosome centromere

Histone H3-variant Cse4-induced positive DNA supercoiling in the yeast plasmid has implications for a plasmid origin of a chromosome centromere

The CENP-A chaperone Scm3 becomes enriched at kinetochores in anaphase independently of CENP-A incorporation

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

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