The CCAN complex: Linking centromere specification to control of kinetochore–microtubule dynamics

McAinsh, Andrew D.; Meraldi, Patrick

doi:10.1016/j.semcdb.2011.09.016

Cited by 44 publications

(34 citation statements)

References 63 publications

(101 reference statements)

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“…CENPA recruits the constitutive centromere-associated network, a 14-component protein complex, to form the inter kinetochore, which provides the structural base for the functional mitotic kinetochore (55). Although Plk1 is implicated in kinetochore function (56), whether Plk1 is involved in kinetochore specification is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Chemical Visualization of Phosphoproteomes on Membrane

Iliuk

Liu

Xue

et al. 2012

Molecular & Cellular Proteomics

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With new discoveries of important roles of phosphorylation on a daily basis, phospho-specific antibodies, as the primary tool for on-membrane detection of phosphoproteins, face enormous challenges. To address an urgent need for convenient and reliable analysis of phosphorylation events, we report a novel strategy for sensitive phosphorylation analysis in the Western blotting format. The chemical reagent, which we termed pIMAGO, is based on a multifunctionalized soluble nanopolymer and is capable of selectively binding to phosphorylated residues independent of amino acid microenvironment, thus offering great promise as a universal tool in biological analyses where the site of phosphorylation is not known or its specific antibody is not available. The specificity and sensitivity of the approach was first examined using a mixture of standard proteins. The method was then applied to monitor phosphorylation changes in in vitro kinase and phosphatase assays. Finally, to demonstrate the unique ability of pIMAGO to measure endogenous phosphorylation, we used it to visualize and determine the differences in phosphorylated proteins that interact with wild-type and kinase dead mutant of Polo-like kinase 1 during mitosis, the results of which were further confirmed by a quantitative phosphoproteomics experiment. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

Chemical Visualization of Phosphoproteomes on Membrane

Iliuk

Liu

Xue

et al. 2012

Molecular & Cellular Proteomics

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“…For example, out of more than 20 proteins that form the constitutive centromere-associated network (CCAN) in mammalian cells, only Cenp-A/Cid and Cenp-C appear to be present in Drosophila and C. elegans (Heeger et al, 2005;Moore and Roth, 2001;Perpelescu and Fukagawa 2011;McAinsh and Meraldi, 2011). Similarly, a Mis18bp homolog cannot be identified in Drosophila, and Cal1 the putative functional Drosophila equivalent of HJURP/Scm3 shares so little sequence similarity that it has been proposed to reflect convergent evolution (Phansalkar et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Distinct modes of centromere protein dynamics during cell cycle progression in Drosophila S2R+ cells

Lidsky

Sprenger

Lehner

2013

Journal of Cell Science

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SummaryCentromeres are specified epigenetically in animal cells. Therefore, faithful chromosome inheritance requires accurate maintenance of epigenetic centromere marks during progression through the cell cycle. Clarification of the mechanisms that control centromere protein behavior during the cell cycle should profit from the relatively simple protein composition of Drosophila centromeres. Thus we have analyzed the dynamics of the three key players Cid/Cenp-A, Cenp-C and Cal1 in S2R+ cells using quantitative microscopy and fluorescence recovery after photobleaching, in combination with novel fluorescent cell cycle markers. As revealed by the observed protein abundances and mobilities, centromeres proceed through at least five distinct states during the cell cycle, distinguished in part by unexpected Cid behavior. In addition to the predominant Cid loading onto centromeres during G1, a considerable but transient increase was detected during early mitosis. A low level of Cid loading was detected in late S and G2, starting at the reported time of centromere DNA replication. Our results reveal the complexities of Drosophila centromere protein dynamics and its intricate coordination with cell cycle progression.

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“…CCAN, a complex of more than a dozen conserved proteins, forms the inner kinetochore, which associates with centromeric chromatin (McAinsh and Meraldi 2011;Westhorpe and Straight 2015). An outer kinetochore network, named KMN for its three major constituents, Knl1, the Mis12 (or MIND) complex, and the Ndc80 complex, mediates the association of the CCAN with spindle microtubules (Cheeseman et al 2006;Santaguida and Musacchio 2009;Foley and Kapoor 2013).…”

Section: Msc1 May Function In Localizing Hdac Activity To Centromeresmentioning

confidence: 99%

“…The constitutive centromere-associated network (CCAN) forms the inner kinetochore and consists of more than a dozen conserved proteins, including fission yeast Mis6 (CENP-I in mammalian cells) that promotes incorporation of CENP-A at the centromere (McAinsh and Meraldi 2011;Westhorpe and Straight 2015). The KMN network is composed of the tethering protein Knl1, the Mis12 complex, and the NDC80 complex, a heterotetramer consisting of Ndc80, Nuf2, Spc24, and Spc25, that links microtubules to the kinetochore (Petrovic et al 2014).…”

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confidence: 99%

Escape from Mitotic Arrest: An Unexpected Connection Between Microtubule Dynamics and Epigenetic Regulation of Centromeric Chromatin in Schizosaccharomyces pombe

George

Walworth

2015

Genetics

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Accurate chromosome segregation is necessary to ensure genomic integrity. Segregation depends on the proper functioning of the centromere, kinetochore, and mitotic spindle microtubules and is monitored by the spindle assembly checkpoint (SAC). In the fission yeast Schizosaccharomyces pombe, defects in Dis1, a microtubule-associated protein that influences microtubule dynamics, lead to mitotic arrest as a result of an active SAC and consequent failure to grow at low temperature. In a mutant dis1 background (dis1-288), loss of function of Msc1, a fission yeast homolog of the KDM5 family of proteins, suppresses the growth defect and promotes normal mitosis. Genetic analysis implicates a histone deacetylase (HDAC)-linked pathway in suppression because HDAC mutants clr6-1, clr3D, and sir2D, though not hos2D, also promote normal mitosis in the dis1-288 mutant. Suppression of the dis phenotype through loss of msc1 function requires the spindle checkpoint protein Mad2 and is limited by the presence of the heterochromatin-associated HP1 protein homolog Swi6. We speculate that alterations in histone acetylation promote a centromeric chromatin environment that compensates for compromised dis1 function by allowing for successful kinetochore-microtubule interactions that can satisfy the SAC. In cells arrested in mitosis by mutation of dis1, loss of function of epigenetic determinants such as Msc1 or specific HDACs can promote cell survival. Because the KDM5 family of proteins has been implicated in human cancers, an appreciation of the potential role of this family of proteins in chromosome segregation is warranted. KEYWORDS Msc1; lysine demethylase KDM5; histone deacetylase (HDAC); Rb; PLU-1; RBP2; trichostatin; thiabendazole; Mad2; Dis1 (XMAP215, TOG1); Swi6 (HP1 homolog) A CCURATE chromosome segregation relies on precise assembly of the multiprotein kinetochore complex, which mediates the link between chromosomes and the mitotic spindle (Przewloka and Glover 2009). The histone H3 variant CENP-A, along with epigenetic marks on canonical histones, defines centromeric chromatin, which forms the template for kinetochore assembly (Allshire and Karpen 2008;Verdaasdonk and Bloom 2011). Kinetochores serve as the site of spindle microtubule attachment (Santaguida and Musacchio 2009) and, along with the centromere, translate microtubule attachment status to mediate force balance, tension sensing, and spindle checkpoint control (Bloom 2014). When associations between chromosomes and the spindle are incorrect, the spindle assembly checkpoint (SAC) delays progression through mitosis by preventing the onset of anaphase (Musacchio and Salmon 2007;Foley and Kapoor 2013).Fission yeast centromeric chromatin (Allshire and Ekwall 2015) consists of a central core (cnt) and internal inverted repeats (imr), defined by the presence of CENP-A and methylated histone H3 K4 chromatin, flanked by heterochromatic outer repeats (otr) marked by methylated histone H3 K9 (Partridge et al. 2000;Takahashi et al. 2000;Kniola et al. 2001). The consti...

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The CCAN complex: Linking centromere specification to control of kinetochore–microtubule dynamics

Cited by 44 publications

References 63 publications

Chemical Visualization of Phosphoproteomes on Membrane

Chemical Visualization of Phosphoproteomes on Membrane

Distinct modes of centromere protein dynamics during cell cycle progression in Drosophila S2R+ cells

Escape from Mitotic Arrest: An Unexpected Connection Between Microtubule Dynamics and Epigenetic Regulation of Centromeric Chromatin in Schizosaccharomyces pombe

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