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      Kinetochore-localized PP1–Sds22 couples chromosome segregation to polar relaxation

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          Abstract

          Cell division requires the precise coordination of chromosome segregation and cytokinesis. This coordination is achieved by the recruitment of an actomyosin regulator, Ect2, to overlapping microtubules at the centre of the elongating anaphase spindle. Ect2 then signals to the overlying cortex to promote the assembly and constriction of an actomyosin ring between segregating chromosomes. Here, by studying division in proliferating Drosophila and human cells, we demonstrate the existence of a second, parallel signalling pathway, which triggers the relaxation of the polar cell cortex at mid anaphase. This is independent of furrow formation, centrosomes and microtubules and, instead, depends on PP1 phosphatase and its regulatory subunit Sds22 (refs 2, 3). As separating chromosomes move towards the polar cortex at mid anaphase, kinetochore-localized PP1-Sds22 helps to break cortical symmetry by inducing the dephosphorylation and inactivation of ezrin/radixin/moesin proteins at cell poles. This promotes local softening of the cortex, facilitating anaphase elongation and orderly cell division. In summary, this identifies a conserved kinetochore-based phosphatase signal and substrate, which function together to link anaphase chromosome movements to cortical polarization, thereby coupling chromosome segregation to cell division.

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          Most cited references29

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          The extracellular matrix guides the orientation of the cell division axis.

          The cell division axis determines the future positions of daughter cells and is therefore critical for cell fate. The positioning of the division axis has been mostly studied in systems such as embryos or yeasts, in which cell shape is well defined. In these cases, cell shape anisotropy and cell polarity affect spindle orientation. It remains unclear whether cell geometry or cortical cues are determinants for spindle orientation in mammalian cultured cells. The cell environment is composed of an extracellular matrix (ECM), which is connected to the intracellular actin cytoskeleton via transmembrane proteins. We used micro-contact printing to control the spatial distribution of the ECM on the substrate and demonstrated that it has a role in determining the orientation of the division axis of HeLa cells. On the basis of our analysis of the average distributions of actin-binding proteins in interphase and mitosis, we propose that the ECM controls the location of actin dynamics at the membrane, and thus the segregation of cortical components in interphase. This segregation is further maintained on the cortex of mitotic cells and used for spindle orientation.
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            Cytokinesis in animal cells.

            Cytokinesis, the final step in cell division, partitions the contents of a single cell into two. In animal cells, cytokinesis occurs through cortical remodeling orchestrated by the anaphase spindle. Cytokinesis relies on a tight interplay between signaling and cellular mechanics and has attracted the attention of both biologists and physicists for more than a century. In this review, we provide an overview of four topics in animal cell cytokinesis: (a) signaling between the anaphase spindle and cortex, (b) the mechanics of cortical remodeling, (c) abscission, and (d) regulation of cytokinesis by the cell cycle machinery. We report on recent progress in these areas and highlight some of the outstanding questions that these findings bring into focus.
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              One-step sequence- and ligation-independent cloning as a rapid and versatile cloning method for functional genomics studies.

              We developed one-step sequence- and ligation-independent cloning (SLIC) as a simple, cost-effective, time-saving, and versatile cloning method. Highly efficient and directional cloning can be achieved by direct bacterial transformation 2.5 min after mixing any linearized vector, an insert(s) prepared by PCR, and T4 DNA polymerase in a tube at room temperature.
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                Author and article information

                Journal
                Nature
                Nature
                Springer Science and Business Media LLC
                0028-0836
                1476-4687
                August 2015
                July 13 2015
                August 2015
                : 524
                : 7566
                : 489-492
                Article
                10.1038/nature14496
                26168397
                bdbe675f-84ff-49cd-b98e-f7b18edc250e
                © 2015

                http://www.springer.com/tdm

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