scholarly journals Cohesin, condensin, and the intramolecular centromere loop together generate the mitotic chromatin spring

2011 ◽  
Vol 193 (7) ◽  
pp. 1167-1180 ◽  
Author(s):  
Andrew D. Stephens ◽  
Julian Haase ◽  
Leandra Vicci ◽  
Russell M. Taylor ◽  
Kerry Bloom
Keyword(s):  
Sister Chromatid ◽  
Protein Complexes ◽  
Spindle Microtubule ◽  
Spindle Axis ◽  
Chromatid Cohesion ◽  
Length Regulation ◽  
Spindle Microtubules ◽  
Mechanistic Basis ◽  
Structural Maintenance Of Chromosomes ◽  
Mitotic Chromatin

Sister chromatid cohesion provides the mechanistic basis, together with spindle microtubules, for generating tension between bioriented chromosomes in metaphase. Pericentric chromatin forms an intramolecular loop that protrudes bidirectionally from the sister chromatid axis. The centromere lies on the surface of the chromosome at the apex of each loop. The cohesin and condensin structural maintenance of chromosomes (SMC) protein complexes are concentrated within the pericentric chromatin, but whether they contribute to tension-generating mechanisms is not known. To understand how pericentric chromatin is packaged and resists tension, we map the position of cohesin (SMC3), condensin (SMC4), and pericentric LacO arrays within the spindle. Condensin lies proximal to the spindle axis and is responsible for axial compaction of pericentric chromatin. Cohesin is radially displaced from the spindle axis and confines pericentric chromatin. Pericentric cohesin and condensin contribute to spindle length regulation and dynamics in metaphase. Together with the intramolecular centromere loop, these SMC complexes constitute a molecular spring that balances spindle microtubule force in metaphase.

Cohesin dependent compaction of mitotic chromosomes

2016 ◽  
Author(s):  
Stephanie A Schalbetter ◽  
Anton Goloborodko ◽  
Geoffrey Fudenberg ◽  
Jon M Belton ◽  
Catrina Miles ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Mitotic Chromosome ◽  
Protein Complexes ◽  
Budding Yeast ◽  
Mitotic Chromosomes ◽  
Chromosome Conformation ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Structural Maintenance Of Chromosomes

Structural Maintenance of Chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply-conserved SMC complexes, organize chromosomes in budding yeast. The canonical role of cohesins is to co-align sister chromatids whilst condensins generally compact mitotic chromosomes. We find strikingly different roles in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosomes arms, independent of and in addition to its role in sister-chromatid cohesion. Cohesin dependent mitotic chromosome compaction can be fully accounted for through cis-looping of chromatin by loop extrusion. Second, condensin is dispensable for compaction along chromosomal arms and instead plays a specialized role, structuring rDNA and peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that SMC-dependent looping is readily deployed in a range of contexts to functionally organize chromosomes.

scholarly journals ConnectingGCN5’s centromeric SAGA to the mitotic tension-sensing checkpoint

2018 ◽  
Vol 29 (18) ◽  
pp. 2201-2212 ◽  
Author(s):  
Emily L. Petty ◽  
Masha Evpak ◽  
Lorraine Pillus
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Spindle Assembly Checkpoint ◽  
Binding Function ◽  
Chromatid Cohesion ◽  
Histone H3 Variant ◽  
Spindle Microtubules ◽  
Low Tension ◽  
Centromere Histone H3 ◽  
Segregation Of Chromosomes

Multiple interdependent mechanisms ensure faithful segregation of chromosomes during cell division. Among these, the spindle assembly checkpoint monitors attachment of spindle microtubules to the centromere of each chromosome, whereas the tension-sensing checkpoint monitors the opposing forces between sister chromatid centromeres for proper biorientation. We report here a new function for the deeply conserved Gcn5 acetyltransferase in the centromeric localization of Rts1, a key player in the tension-sensing checkpoint. Rts1 is a regulatory component of protein phopshatase 2A, a near universal phosphatase complex, which is recruited to centromeres by the Shugoshin (Sgo) checkpoint component under low-tension conditions to maintain sister chromatid cohesion. We report that loss of Gcn5 disrupts centromeric localization of Rts1. Increased RTS1 dosage robustly suppresses gcn5∆ cell cycle and chromosome segregation defects, including restoration of Rts1 to centromeres. Sgo1’s Rts1-binding function also plays a key role in RTS1 dosage suppression of gcn5∆ phenotypes. Notably, we have identified residues of the centromere histone H3 variant Cse4 that function in these chromosome segregation-related roles of RTS1. Together, these findings expand the understanding of the mechanistic roles of Gcn5 and Cse4 in chromosome segregation.

Organization of Chromosomal DNA by SMC Complexes

2019 ◽  
Vol 53 (1) ◽  
pp. 445-482 ◽  
Author(s):  
Stanislau Yatskevich ◽  
James Rhodes ◽  
Kim Nasmyth
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Mitotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Chromosomal Dna ◽  
Chromosome Architecture ◽  
Chromatid Cohesion ◽  
Dna Translocases ◽  
Structural Maintenance Of Chromosomes

Structural maintenance of chromosomes (SMC) complexes are key organizers of chromosome architecture in all kingdoms of life. Despite seemingly divergent functions, such as chromosome segregation, chromosome maintenance, sister chromatid cohesion, and mitotic chromosome compaction, it appears that these complexes function via highly conserved mechanisms and that they represent a novel class of DNA translocases.

scholarly journals Cohesins Determine the Attachment Manner of Kinetochores to Spindle Microtubules at Meiosis I in Fission Yeast

2003 ◽  
Vol 23 (11) ◽  
pp. 3965-3973 ◽  
Author(s):  
Shihori Yokobayashi ◽  
Masayuki Yamamoto ◽  
Yoshinori Watanabe
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Specific Requirement ◽  
Spindle Poles ◽  
Chromatid Cohesion ◽  
Spindle Microtubules ◽  
Yeast Meiosis ◽  
Meiosis I ◽  
Random Division

ABSTRACT During mitosis, sister kinetochores attach to microtubules that extend to opposite spindle poles (bipolar attachment) and pull the chromatids apart at anaphase (equational segregation). A multisubunit complex called cohesin, including Rad21/Scc1, plays a crucial role in sister chromatid cohesion and equational segregation at mitosis. Meiosis I differs from mitosis in having a reductional pattern of chromosome segregation, in which sister kinetochores are attached to the same spindle (monopolar attachment). During meiosis, Rad21/Scc1 is largely replaced by its meiotic counterpart, Rec8. If Rec8 is inactivated in fission yeast, meiosis I is shifted from reductional to equational division. However, the reason rec8Δ cells undergo equational rather than random division has not been clarified; therefore, it has been unclear whether equational segregation is due to a loss of cohesin in general or to a loss of a specific requirement for Rec8. We report here that the equational segregation at meiosis I depends on substitutive Rad21, which relocates to the centromeres if Rec8 is absent. Moreover, we demonstrate that even if sufficient amounts of Rad21 are transferred to the centromeres at meiosis I, thereby establishing cohesion at the centromeres, rec8Δ cells never recover monopolar attachment but instead secure bipolar attachment. Thus, Rec8 and Rad21 define monopolar and bipolar attachment, respectively, at meiosis I. We conclude that cohesin is a crucial determinant of the attachment manner of kinetochores to the spindle microtubules at meiosis I in fission yeast.

scholarly journals Bub1 is essential for assembly of the functional inner centromere

2007 ◽  
Vol 176 (7) ◽  
pp. 919-928 ◽  
Author(s):  
Yekaterina Boyarchuk ◽  
Adrian Salic ◽  
Mary Dasso ◽  
Alexei Arnaoutov
Keyword(s):  
Sister Chromatid ◽  
Kinase Activity ◽  
Centromeric Region ◽  
Protein Complexes ◽  
Multiple Points ◽  
Biochemical Pathways ◽  
Microtubule Attachment ◽  
Egg Extract ◽  
Chromatid Cohesion ◽  
Chromosomal Passenger

During mitosis, the inner centromeric region (ICR) recruits protein complexes that regulate sister chromatid cohesion, monitor tension, and modulate microtubule attachment. Biochemical pathways that govern formation of the inner centromere remain elusive. The kinetochore protein Bub1 was shown to promote assembly of the outer kinetochore components, such as BubR1 and CENP-F, on centromeres. Bub1 was also implicated in targeting of Shugoshin (Sgo) to the ICR. We show that Bub1 works as a master organizer of the ICR. Depletion of Bub1 from Xenopus laevis egg extract or from HeLa cells resulted in both destabilization and displacement of chromosomal passenger complex (CPC) from the ICR. Moreover, soluble Bub1 controls the binding of Sgo to chromatin, whereas the CPC restricts loading of Sgo specifically onto centromeres. We further provide evidence that Bub1 kinase activity is pivotal for recruitment of all of these components. Together, our findings demonstrate that Bub1 acts at multiple points to assure the correct kinetochore formation.

scholarly journals Condensin and cohesin display different arm conformations with characteristic hinge angles

2002 ◽  
Vol 156 (3) ◽  
pp. 419-424 ◽  
Author(s):  
David E. Anderson ◽  
Ana Losada ◽  
Harold P. Erickson ◽  
Tatsuya Hirano
Keyword(s):  
Catalytic Domain ◽  
Protein Complexes ◽  
Coiled Coil ◽  
Coiled Coils ◽  
Structure Characteristic ◽  
Catalytic Domains ◽  
Open Conformation ◽  
Chromatid Cohesion ◽  
Structural Maintenance Of Chromosomes ◽  
Smc Proteins

Structural maintenance of chromosomes (SMC) proteins play central roles in higher-order chromosome dynamics from bacteria to humans. In eukaryotes, two different SMC protein complexes, condensin and cohesin, regulate chromosome condensation and sister chromatid cohesion, respectively. Each of the complexes consists of a heterodimeric pair of SMC subunits and two or three non-SMC subunits. Previous studies have shown that a bacterial SMC homodimer has a symmetrical structure in which two long coiled-coil arms are connected by a flexible hinge. A catalytic domain with DNA- and ATP-binding activities is located at the distal end of each arm. We report here the visualization of vertebrate condensin and cohesin by electron microscopy. Both complexes display the two-armed structure characteristic of SMC proteins, but their conformations are remarkably different. The hinge of condensin is closed and the coiled-coil arms are placed close together. In contrast, the hinge of cohesin is wide open and the coiled-coils are spread apart from each other. The non-SMC subunits of both condensin and cohesin form a globular complex bound to the catalytic domains of the SMC heterodimers. We propose that the “closed” conformation of condensin and the “open” conformation of cohesin are important structural properties that contribute to their specialized biochemical and physiological functions.

scholarly journals Shugoshin protects cohesin complexes at centromeres

2005 ◽  
Vol 360 (1455) ◽  
pp. 515-521 ◽  
Author(s):  
Yoshinori Watanabe ◽  
Tomoya S Kitajima
Keyword(s):  
Fission Yeast ◽  
Sister Chromatid ◽  
Crucial Role ◽  
Regional Difference ◽  
Sister Chromatid Cohesion ◽  
Protein Family ◽  
Chromatid Cohesion ◽  
Spindle Microtubules ◽  
Pulling Force ◽  
Eukaryotic Organisms

The different regulation of sister chromatid cohesion at centromeres and along chromosome arms is obvious during meiosis, because centromeric cohesion, but not arm cohesion, persists throughout anaphase of the first division. A protein required to protect centromeric cohesin Rec8 from separase cleavage has been identified and named shugoshin (or Sgo1) after shugoshin (‘guardian spirit’ in Japanese). It has become apparent that shugoshin shows marginal homology with Drosophila Mei-S332 and several uncharacterized proteins in other eukaryotic organisms. Because Mei-S332 is a protein previously shown to be required for centromeric cohesion in meiosis, it is now established that shugoshin represents a conserved protein family defined as a centromeric protector of Rec8 cohesin complexes in meiosis. The regional difference of sister chromatid cohesion is also observed during mitosis in vertebrates; the cohesion is much more robust at the centromere at metaphase, where it antagonizes the pulling force of spindle microtubules that attach the kinetochores from opposite poles. The human shugoshin homologue (hSgo1) is required to protect the centromeric localization of the mitotic cohesin, Scc1, until metaphase. Bub1 plays a crucial role in the localization of shugoshin to centromeres in both fission yeast and humans.

scholarly journals SMC Complexes Are Guarded by the SUMO Protease Ulp2 Against SUMO-Chain-Mediated Turnover

2020 ◽  
Author(s):  
Ivan Psakhye ◽  
Dana Branzei
Keyword(s):  
Dna Repair ◽  
Ubiquitin Ligase ◽  
Sister Chromatid ◽  
Essential Role ◽  
Sumo Protease ◽  
Chromatid Cohesion ◽  
Multiple Processes ◽  
Simultaneous Loss ◽  
Structural Maintenance Of Chromosomes

ABSTRACTStructural maintenance of chromosomes (SMC) complexes, cohesin, condensin and Smc5/6, are essential for viability and participate in multiple processes, including sister chromatid cohesion, chromosome condensation, and DNA repair. Here we show that SUMO chains target all three SMC complexes and are antagonized by the SUMO protease Ulp2 to prevent their turnover. We uncover that the essential role of the cohesin-associated subunit Pds5 is to counteract SUMO chains jointly with Ulp2. Importantly, fusion of Ulp2 to kleisin Scc1 supports viability of PDS5 null cells and protects cohesin from proteasomal degradation mediated by the SUMO-targeted ubiquitin ligase Slx5/Slx8. The lethality of PDS5 deleted cells can also be bypassed by simultaneous loss of the PCNA unloader, Elg1, and the cohesin releaser, Wpl1, but only when Ulp2 is functional. Condensin and Smc5/6 complex are similarly guarded by Ulp2 against unscheduled SUMO-chain assembly, which we propose to time the availability of SMC complexes on chromatin.

scholarly journals Conserved roles of chromatin remodellers in cohesin loading onto chromatin

2020 ◽  
Vol 66 (5) ◽  
pp. 951-956
Author(s):  
Sofía Muñoz ◽  
Francesca Passarelli ◽  
Frank Uhlmann
Keyword(s):  
Sister Chromatid ◽  
Domain Architecture ◽  
Sister Chromatid Cohesion ◽  
Chromatin Domain ◽  
Dual Function ◽  
Chromatin Remodelers ◽  
Chromatid Cohesion ◽  
Highly Expressed Genes ◽  
Structural Maintenance Of Chromosomes

Abstract Cohesin is a conserved, ring-shaped protein complex that topologically entraps DNA. This ability makes this member of the structural maintenance of chromosomes (SMC) complex family a central hub of chromosome dynamics regulation. Besides its essential role in sister chromatid cohesion, cohesin shapes the interphase chromatin domain architecture and plays important roles in transcriptional regulation and DNA repair. Cohesin is loaded onto chromosomes at centromeres, at the promoters of highly expressed genes, as well as at DNA replication forks and sites of DNA damage. However, the features that determine these binding sites are still incompletely understood. We recently described a role of the budding yeast RSC chromatin remodeler in cohesin loading onto chromosomes. RSC has a dual function, both as a physical chromatin receptor of the Scc2/Scc4 cohesin loader complex, as well as by providing a nucleosome-free template for cohesin loading. Here, we show that the role of RSC in sister chromatid cohesion is conserved in fission yeast. We discuss what is known about the broader conservation of the contribution of chromatin remodelers to cohesin loading onto chromatin.

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