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      The Centromere: Chromatin Foundation for the Kinetochore Machinery

      review-article
      1 , , 2 , ∗∗
      Developmental Cell
      Cell Press

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          Abstract

          Since discovery of the centromere-specific histone H3 variant CENP-A, centromeres have come to be defined as chromatin structures that establish the assembly site for the complex kinetochore machinery. In most organisms, centromere activity is defined epigenetically, rather than by specific DNA sequences. In this review, we describe selected classic work and recent progress in studies of centromeric chromatin with a focus on vertebrates. We consider possible roles for repetitive DNA sequences found at most centromeres, chromatin factors and modifications that assemble and activate CENP-A chromatin for kinetochore assembly, plus the use of artificial chromosomes and kinetochores to study centromere function.

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          Most cited references163

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          Cohesin: its roles and mechanisms.

          The cohesin complex is a major constituent of interphase and mitotic chromosomes. Apart from its role in mediating sister chromatid cohesion, it is also important for DNA double-strand-break repair and transcriptional control. The functions of cohesin are regulated by phosphorylation, acetylation, ATP hydrolysis, and site-specific proteolysis. Recent evidence suggests that cohesin acts as a novel topological device that traps chromosomal DNA within a large tripartite ring formed by its core subunits.
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            The conserved KMN network constitutes the core microtubule-binding site of the kinetochore.

            The microtubule-binding interface of the kinetochore is of central importance in chromosome segregation. Although kinetochore components that stabilize, translocate on, and affect the polymerization state of microtubules have been identified, none have proven essential for kinetochore-microtubule interactions. Here, we examined the conserved KNL-1/Mis12 complex/Ndc80 complex (KMN) network, which is essential for kinetochore-microtubule interactions in vivo. We identified two distinct microtubule-binding activities within the KMN network: one associated with the Ndc80/Nuf2 subunits of the Ndc80 complex, and a second in KNL-1. Formation of the complete KMN network, which additionally requires the Mis12 complex and the Spc24/Spc25 subunits of the Ndc80 complex, synergistically enhances microtubule-binding activity. Phosphorylation by Aurora B, which corrects improper kinetochore-microtubule connections in vivo, reduces the affinity of the Ndc80 complex for microtubules in vitro. Based on these findings, we propose that the conserved KMN network constitutes the core microtubule-binding site of the kinetochore.
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              Genome sequence, comparative analysis, and population genetics of the domestic horse.

              We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
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                Author and article information

                Contributors
                Journal
                Dev Cell
                Dev. Cell
                Developmental Cell
                Cell Press
                1534-5807
                1878-1551
                08 September 2014
                08 September 2014
                : 30
                : 5
                : 496-508
                Affiliations
                [1 ]Department of Molecular Genetics, National Institute of Genetics and Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan
                [2 ]Wellcome Trust Centre for Cell Biology, University of Edinburgh, King’s Buildings, Mayfield Road, Edinburgh, EH9 3JR, UK
                Author notes
                []Corresponding author tfukagaw@ 123456lab.nig.ac.jp
                [∗∗ ]Corresponding author bill.earnshaw@ 123456ed.ac.uk
                Article
                S1534-5807(14)00546-2
                10.1016/j.devcel.2014.08.016
                4160344
                25203206
                f520cdfe-2373-4105-bda6-5b64e8cbd69b
                © 2014 The Authors
                History
                Categories
                Review

                Developmental biology
                Developmental biology

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