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      Chromosome Segregation in Budding Yeast: Sister Chromatid Cohesion and Related Mechanisms

      research-article
      Genetics
      Genetics Society of America
      Keyords placeholder, Mitosis, Meiosis, Chromosome, Cohesin, Segregation

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          Abstract

          Studies on budding yeast have exposed the highly conserved mechanisms by which duplicated chromosomes are evenly distributed to daughter cells at the metaphase–anaphase transition. The establishment of proteinaceous bridges between sister chromatids, a function provided by a ring-shaped complex known as cohesin, is central to accurate segregation. It is the destruction of this cohesin that triggers the segregation of chromosomes following their proper attachment to microtubules. Since it is irreversible, this process must be tightly controlled and driven to completion. Furthermore, during meiosis, modifications must be put in place to allow the segregation of maternal and paternal chromosomes in the first division for gamete formation. Here, I review the pioneering work from budding yeast that has led to a molecular understanding of the establishment and destruction of cohesion.

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          Most cited references350

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          The spindle-assembly checkpoint in space and time.

          In eukaryotes, the spindle-assembly checkpoint (SAC) is a ubiquitous safety device that ensures the fidelity of chromosome segregation in mitosis. The SAC prevents chromosome mis-segregation and aneuploidy, and its dysfunction is implicated in tumorigenesis. Recent molecular analyses have begun to shed light on the complex interaction of the checkpoint proteins with kinetochores--structures that mediate the binding of spindle microtubules to chromosomes in mitosis. These studies are finally starting to reveal the mechanisms of checkpoint activation and silencing during mitotic progression.
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            Cohesins: chromosomal proteins that prevent premature separation of sister chromatids.

            Cohesion between sister chromatids opposes the splitting force exerted by microtubules, and loss of this cohesion is responsible for the subsequent separation of sister chromatids during anaphase. We describe three chromosmal proteins that prevent premature separation of sister chromatids in yeast. Two, Smc1p and Smc3p, are members of the SMC family, which are putative ATPases with coiled-coil domains. A third protein, which we call Scc1p, binds to chromosomes during S phase, dissociates from them at the metaphase-to-anaphase transition, and is degraded by the anaphase promoting complex. Association of Scc1p with chromatin depends on Smc1p. Proteins homologous to Scc1p exist in a variety of eukaryotic organisms including humans. A common cohesion apparatus might be used by all eukaryotic cells during both mitosis and meiosis.
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              Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends.

              Formation of single-strand DNA (ssDNA) tails at a double-strand break (DSB) is a key step in homologous recombination and DNA-damage signaling. The enzyme(s) producing ssDNA at DSBs in eukaryotes remain unknown. We monitored 5'-strand resection at inducible DSB ends in yeast and identified proteins required for two stages of resection: initiation and long-range 5'-strand resection. We show that the Mre11-Rad50-Xrs2 complex (MRX) initiates 5' degradation, whereas Sgs1 and Dna2 degrade 5' strands exposing long 3' strands. Deletion of SGS1 or DNA2 reduces resection and DSB repair by single-strand annealing between distant repeats while the remaining long-range resection activity depends on the exonuclease Exo1. In exo1Deltasgs1Delta double mutants, the MRX complex together with Sae2 nuclease generate, in a stepwise manner, only few hundred nucleotides of ssDNA at the break, resulting in inefficient gene conversion and G2/M damage checkpoint arrest. These results provide important insights into the early steps of DSB repair in eukaryotes.
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                Author and article information

                Journal
                Genetics
                Genetics
                genetics
                genetics
                genetics
                Genetics
                Genetics Society of America
                0016-6731
                1943-2631
                January 2014
                January 2014
                January 2014
                : 196
                : 1
                : 31-63
                Affiliations
                [1]The Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom
                Author notes
                Address for correspondence: School of Biological Sciences, Michael Swann Building, Mayfield Rd., Edinburgh EH9 3JR, United Kingdom. E-mail: adele.marston@ 123456ed.ac.uk
                Article
                145144
                10.1534/genetics.112.145144
                3872193
                24395824
                7af3d2fa-c62d-457e-a6d4-c3ef972dcfa4
                Copyright © 2014 by the Genetics Society of America

                Available freely online through the author-supported open access option.

                History
                : 24 July 2013
                : 18 September 2013
                Page count
                Pages: 33
                Categories
                YeastBook
                Cell Cycle
                Custom metadata
                v1

                Genetics
                mitosis,meiosis,cohesin,keyords placeholder,chromosome,segregation
                Genetics
                mitosis, meiosis, cohesin, keyords placeholder, chromosome, segregation

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