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      Shugoshins: Tension-Sensitive Pericentromeric Adaptors Safeguarding Chromosome Segregation

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      Molecular and Cellular Biology
      American Society for Microbiology

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          Abstract

          The shugoshin/Mei-S332 family are proteins that associate with the chromosomal region surrounding the centromere (the pericentromere) and that play multiple and distinct roles in ensuring the accuracy of chromosome segregation during both mitosis and meiosis. The underlying role of shugoshins appears to be to serve as pericentromeric adaptor proteins that recruit several different effectors to this region of the chromosome to regulate processes critical for chromosome segregation. Crucially, shugoshins undergo changes in their localization in response to the tension that is exerted on sister chromosomes by the forces of the spindle that will pull them apart. This has led to the idea that shugoshins provide a platform for activities required at the pericentromere only when sister chromosomes lack tension. Conversely, disassembly of the shugoshin pericentromeric platform may provide a signal that sister chromosomes are under tension. Here the functions and regulation of these important tension-sensitive pericentromeric proteins are discussed.

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          Most cited references145

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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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            Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore.

            In eukaryotes, chromosome segregation during cell division is facilitated by the kinetochore, a multiprotein structure that is assembled on centromeric DNA. The kinetochore attaches chromosomes to spindle microtubules, modulates the stability of these attachments and relays the microtubule-binding status to the spindle assembly checkpoint (SAC), a cell cycle surveillance pathway that delays chromosome segregation in response to unattached kinetochores. Recent studies are shaping current thinking on how each of these kinetochore-centred processes is achieved, and how their integration ensures faithful chromosome segregation, focusing on the essential roles of kinase-phosphatase signalling and the microtubule-binding KMN protein network.
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              Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2 and Scc4 proteins.

              Cohesion between sister chromatids depends on a multisubunit cohesin complex that binds to chromosomes around DNA replication and dissociates from them at the onset of anaphase. Scc2p, though not a cohesin subunit, is also required for sister chromatid cohesion. We show here that Scc2p forms a complex with a novel protein, Scc4p, which is also necessary for sister cohesion. In scc2 or scc4 mutants, cohesin complexes form normally but fail to bind both to centromeres and to chromosome arms. Our data suggest that a major role for the Scc2p/Scc4p complex is to facilitate the loading of cohesin complexes onto chromosomes.
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                Author and article information

                Journal
                Mol Cell Biol
                Mol. Cell. Biol
                mcb
                mcb
                MCB
                Molecular and Cellular Biology
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                0270-7306
                1098-5549
                1 December 2014
                February 2015
                1 December 2014
                : 35
                : 4
                : 634-648
                Affiliations
                The Wellcome Trust Centre for Cell Biology, School of Biological Sciences, Edinburgh, United Kingdom
                Author notes
                Address correspondence to adele.marston@ 123456ed.ac.uk .

                Citation Marston AL. 2015. Shugoshins: tension-sensitive pericentromeric adaptors safeguarding chromosome segregation. Mol Cell Biol 35:634–648. doi: 10.1128/MCB.01176-14.

                Article
                01176-14
                10.1128/MCB.01176-14
                4301718
                25452306
                fb27ca90-79bd-4b4b-a0a9-2874ac51fb2f
                Copyright © 2015 Marston

                This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.

                History
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 154, Pages: 15, Words: 12985
                Categories
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                Molecular biology
                Molecular biology

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