The ABCs of CENPs

Perpelescu, Marinela; Fukagawa, Tatsuo

doi:10.1007/s00412-011-0330-0

Cited by 180 publications

(187 citation statements)

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“…However, this tethering does not serve to recruit the Ndc80 complex during kinetochore assembly as cells lacking Cnn1 do not suffer from reduced levels of the Ndc80 complex, nor a reduction in the Mtw1 and Spc105 complexes (Bock et al 2012). In contrast, mammalian CENP-T actively recruits the Ndc80 complex to CENs (Gascoigne et al 2011) and the middle region of CENP-T appears to be flexible and assists in kinetochore stretching when it undergoes tension (Perpelescu and Fukagawa 2011;Suzuki et al 2011;Westhorpe and Straight 2013). Similarly, the preanaphase Cnn1 linkages may allow a proper intrakinetochore stretch required for chromosome biorientation, as shown for CENP-T (Suzuki et al 2014).…”

Section: Discussionmentioning

confidence: 99%

The Mps1 Kinase Modulates the Recruitment and Activity of Cnn1CENP-T at Saccharomyces cerevisiae Kinetochores

et al. 2015

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Kinetochores are conserved protein complexes that bind the replicated chromosomes to the mitotic spindle and then direct their segregation. To better comprehend Saccharomyces cerevisiae kinetochore function, we dissected the phospho-regulated dynamic interaction between conserved kinetochore protein Cnn1 CENP-T , the centromere region, and the Ndc80 complex through the cell cycle. Cnn1 localizes to kinetochores at basal levels from G1 through metaphase but accumulates abruptly at anaphase onset. How Cnn1 is recruited and which activities regulate its dynamic localization are unclear. We show that Cnn1 harbors two kinetochore-localization activities: a C-terminal histone-fold domain (HFD) that associates with the centromere region and a N-terminal Spc24/Spc25 interaction sequence that mediates linkage to the microtubule-binding Ndc80 complex. We demonstrate that the established Ndc80 binding site in the N terminus of Cnn1, Cnn1 , should be extended with flanking residues, Cnn1 , to allow near maximal binding affinity to Ndc80. Cnn1 localization was proposed to depend on Mps1 kinase activity at Cnn1-S74, based on in vitro experiments demonstrating the Cnn1-Ndc80 complex interaction. We demonstrate that from G1 through metaphase, Cnn1 localizes via both its HFD and N-terminal Spc24/Spc25 interaction sequence, and deletion or mutation of either region results in anomalous Cnn1 kinetochore levels. At anaphase onset (when Mps1 activity decreases) Cnn1 becomes enriched mainly via the N-terminal Spc24/Spc25 interaction sequence. In sum, we provide the first in vivo evidence of Cnn1 preanaphase linkages with the kinetochore and enrichment of the linkages during anaphase. KEYWORDS Cnn1; Mps1; kinetochore; centromere; CENP-T K INETOCHORES are large protein structures that assemble hierarchically on the centromeres (CEN) of replicated chromosomes (sister chromatids). They biorient each sister chromatid pair to the microtubules (MTs) of the mitotic spindle and orchestrate chromatid segregation into the daughter cells (Cheeseman 2014;Malvezzi and Westermann 2014). At the core of each kinetochore lies a protein network named KMN (KLN1/Spc105, MIS12/Mtw1, and NDC80/Ndc80 complexes) that bridges the CEN and MTs (Cheeseman et al. 2006;Westermann et al. 2007). The Ndc80 complex attaches kinetochores to the MTs via its outer Ndc80/Nuf2 dimer (Wei et al. 2007;Ciferri et al. 2008;Alushin et al. 2010), while its CEN-proximal Spc24/Spc25 dimer interacts with a putatively CEN-associated protein, known as Cnn1 in budding yeast (CENP-T in metazoans). The N-terminal domain of Cnn1 and CENP-T hook onto the interface of the Spc24/Spc25 dimer (Malvezzi et al. 2013;Nishino et al. 2013). In its C terminus, Cnn1 harbors a histonefold domain (HFD) (Schleiffer et al. 2012), which may associate with CEN DNA, as does CENP-T (Hori et al. 2008;Nishino et al. 2012).Cnn1 levels at kinetochores are low from G1 through metaphase but increase two-to threefold at anaphase entry and drop back to base level at anaphase exit. Cnn1 interacts with the...

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Section: Discussionmentioning

confidence: 99%

The Mps1 Kinase Modulates the Recruitment and Activity of Cnn1CENP-T at Saccharomyces cerevisiae Kinetochores

et al. 2015

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“…While the canonical nucleosome is typical in most eukaryotic chromatin, the nucleosomes in eukaryotic centromeres are known to also include a centromere-specific histone H3 variant, called CENH3 ( Figure 2). CENH3 defines the functional centromeres upon which the kinetochore is established (Perpelescu and Fukagawa, 2011). Any alteration of the centromere structural components could have devastating effects on the fidelity of cell division and overall organismal viability.…”

Section: The Centromere As a New Target For Plant Improvementmentioning

confidence: 99%

Modification of centromere structure: a promising approach for haploidline production in plant breeding

Tek¹,

Stupar²,

Nagaki³

2015

Turk J Agric For

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Breeding based on doubled-haploid approaches has recently become a common tool for accelerating crop improvement in many plant species. However, many plant species do not have a reliable method for haploid induction. A promising new approach involving centromere engineering has recently been proposed to overcome this limitation. Here we provide a perspective of this novel method for the production of haploid plants, which was originally described in the model plant species Arabidopsis thaliana. Centromeres, known to be critical for the accurate distribution of chromosomes in every cell division, have now become a novel target for crop improvement by enabling doubled-haploid technologies.

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“…The CCAN components have been identified through extensive biochemical studies and cellular localization analyses (Obuse et al, 2004;Foltz et al, 2006;Izuta et al, 2006;Okada et al, 2006). They are represented by CENP-C, -H, -I, -K to -U, -W and -X, which can be further categorized into subgroups based on interaction studies performed in chicken and human cell lines (Cheeseman and Desai, 2008;Perpelescu and Fukagawa, 2011). Most CCAN proteins are conserved in fission yeast, but surprisingly no CCAN constituent, apart from CENP-C, has been identified in fruit flies or nematodes (Perpelescu and Fukagawa, 2011) (Table 1).…”

Section: Dna-proximal Members Of Ccanmentioning

confidence: 99%

“…These proteins are characterized as CCAN members that are more intimately related to CENP-Anucleosomes. A number of other factors can also be found in close proximity to CENP-A, including CENP-B, HJURP, nucleophosmin and a general nucleosome remodeler FACT (Cheeseman and Desai, 2008;Perpelescu and Fukagawa, 2011).…”

Section: Dna-proximal Members Of Ccanmentioning

confidence: 99%

The smooth and stable operation of centromeres

Ogiyama

Ishii

2012

Genes Genet. Syst.

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The centromere functions as a unique chromosomal attachment site for microtubules. Appropriate microtubule attachment is fundamental for organized chromosome behavior during mitosis and meiosis. Hence, centromeres must function both smoothly and stably. However, centromeric DNA sequences are poorly conserved between species despite common functions and similar centromeric protein composition, which leads us to the question: how are centromeres established and maintained? In this review, we summarize the recent progress in deciphering the mechanisms of centromere function. Specifically, we focus our attention on mechanisms closely-related to centromeric DNA and chromatin. By gathering such information, we hope to reveal a new dimension to the true nature of centromeres.

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The ABCs of CENPs

Cited by 180 publications

References 184 publications

The Mps1 Kinase Modulates the Recruitment and Activity of Cnn1CENP-T at Saccharomyces cerevisiae Kinetochores

The Mps1 Kinase Modulates the Recruitment and Activity of Cnn1CENP-T at Saccharomyces cerevisiae Kinetochores

Modification of centromere structure: a promising approach for haploidline production in plant breeding

The smooth and stable operation of centromeres

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