scholarly journals Additional copies of the NOG2 and IST2 genes suppress the deficiency of cohesin Irr1p/Scc3p in Saccharomyces cerevisiae.

2002 ◽  
Vol 49 (2) ◽  
pp. 421-425 ◽  
Author(s):  
Agnieszka Białkowska ◽  
Anna Kurlandzka
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Division ◽  
Sister Chromatid ◽  
Colony Formation ◽  
Ribosomal Subunit ◽  
Mitotic Cell ◽  
Solid Support ◽  
Mrna Splicing ◽  
Cohesin Complex ◽  
Chromatid Cohesion

The protein encoded by the IRR1/SCC3 gene is an element of the cohesin complex of Saccharomyces cerevisiae, responsible for establishing and maintaining sister chromatid cohesion during mitotic cell division. We noticed previously that lowering the level of expression of IRR1/SCC3 affects colony formation on solid support. Here we describe two dosage suppressors (IST2, NOG2) overcoming the inability to form colonies of an Irr1p-deficient strain. Ist2 is probably involved in osmotolerance, Nog2p is a putative GTPase required for 60S ribosomal subunit maturation, but may also participate in mRNA splicing.

scholarly journals Absence of the Spindle Assembly Checkpoint restores mitotic fidelity upon loss of sister chromatid cohesion

2018 ◽  
Author(s):  
Rui D. Silva ◽  
Mihailo Mirkovic ◽  
Leonardo G. Guilgur ◽  
Om S. Rathore ◽  
Rui Gonçalo Martinho ◽  
...  
Keyword(s):  
Cell Survival ◽  
Sister Chromatid ◽  
Spindle Assembly Checkpoint ◽  
Genome Shuffling ◽  
Spindle Assembly ◽  
Sister Chromatid Cohesion ◽  
Abnormal Development ◽  
Wing Development ◽  
Cohesin Complex ◽  
Chromatid Cohesion

AbstractSister chromatid cohesion is essential for faithful mitosis, as premature cohesion loss leads to random chromosome segregation and aneuploidy, resulting in abnormal development. To identify specific conditions capable of restoring defects associated with cohesion loss, we screened for genes whose depletion modulates Drosophila wing development when sister chromatid cohesion is impaired. Cohesion deficiency was induced by knock-down of the acetyltransferase Separation anxiety (San)/Naa50, a cohesin complex stabilizer. Several genes whose function impacts wing development upon cohesion loss were identified. Surprisingly, knockdown of key Spindle Assembly Checkpoint (SAC) proteins, Mad2 and Mps1, suppressed developmental defects associated with San depletion. SAC impairment upon cohesin removal, triggered by San depletion or artificial removal of the cohesin complex, prevented extensive genome shuffling, reduced segregation defects and restored cell survival. This counterintuitive phenotypic suppression was caused by an intrinsic bias for efficient chromosome bi-orientation at mitotic entry, coupled with slow engagement of error-correction reactions. We conclude that mitotic timing determines the severity of defects associated with cohesion deficiency. Therefore, although divisions are still error-prone, SAC inactivation enhances cell survival and tissue homeostasis upon cohesion loss.

scholarly journals Scc2/Nipbl hops between chromosomal cohesin rings after loading

2017 ◽  
Author(s):  
James D.P. Rhodes ◽  
Davide Mazza ◽  
Kim A. Nasmyth ◽  
Stephan Uphoff
Keyword(s):  
Single Molecule ◽  
Sister Chromatid ◽  
Fluorescence Recovery After Photobleaching ◽  
Sister Chromatid Cohesion ◽  
Dna Looping ◽  
Cohesin Complex ◽  
Single Molecule Tracking ◽  
Loading Function ◽  
Stop And Go ◽  
Chromatid Cohesion

AbstractThe cohesin complex mediates DNA-DNA interactions both between (sister chromatid cohesion) and within chromosomes (DNA looping) via a process thought to involve entrapment of DNAs within its tripartite ring. It has been suggested that intra- chromosome loops are generated through processive extrusion of DNAs through the lumen of cohesin’s ring. Scc2 (Nipbl) is essential for loading cohesin onto chromosomes but not for maintaining sister chromatid cohesion following DNA replication. It has therefore been assumed that Scc2 is involved exclusively in the cohesin loading process. However, it is possible that the stimulation of cohesin’s ABC-like ATPase by Scc2 also has a post-loading function, for example driving loop extrusion. Using fluorescence recovery after photobleaching (FRAP) and single-molecule tracking, we show that Scc2 binds dynamically to chromatin, principally through an association with cohesin. Scc2’s movement within chromatin is consistent with a “stop-and-go” or “hopping” motion. We suggest that a low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading.

scholarly journals Chromosome interaction over a distance in meiosis

2015 ◽  
Vol 2 (2) ◽  
pp. 150029 ◽  
Author(s):  
Mary Brady ◽  
Leocadia V. Paliulis
Keyword(s):  
Cell Division ◽  
Sex Chromosomes ◽  
Sister Chromatid ◽  
Daughter Cell ◽  
Sister Chromatid Cohesion ◽  
Sister Chromatids ◽  
Physical Connection ◽  
Chromatid Cohesion ◽  
Different Types ◽  
Random Segregation

The challenge of cell division is to distribute partner chromosomes (pairs of homologues, pairs of sex chromosomes or pairs of sister chromatids) correctly, one into each daughter cell. In the ‘standard’ meiosis, this problem is solved by linking partners together via a chiasma and/or sister chromatid cohesion, and then separating the linked partners from one another in anaphase; thus, the partners are kept track of, and correctly distributed. Many organisms, however, properly separate chromosomes in the absence of any obvious physical connection, and movements of unconnected partner chromosomes are coordinated at a distance. Meiotic distance interactions happen in many different ways and in different types of organisms. In this review, we discuss several different known types of distance segregation and propose possible explanations for non-random segregation of distance-segregating chromosomes.

scholarly journals Pds5p regulates the maintenance of sister chromatid cohesion and is sumoylated to promote the dissolution of cohesion

2003 ◽  
Vol 163 (4) ◽  
pp. 729-741 ◽  
Author(s):  
Kristen Stead ◽  
Cristina Aguilar ◽  
Theresa Hartman ◽  
Melissa Drexel ◽  
Pamela Meluh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Temperature Sensitivity ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Cohesin Complex ◽  
Chromatid Cohesion ◽  
Chromosomal Loci

Pds5p and the cohesin complex are required for sister chromatid cohesion and localize to the same chromosomal loci over the same cell cycle window. However, Pds5p and the cohesin complex likely have distinct roles in cohesion. We report that pds5 mutants establish cohesion, but during mitosis exhibit precocious sister dissociation. Thus, unlike the cohesin complex, which is required for cohesion establishment and maintenance, Pds5p is required only for maintenance. We identified SMT4, which encodes a SUMO isopeptidase, as a high copy suppressor of both the temperature sensitivity and precocious sister dissociation of pds5 mutants. In contrast, SMT4 does not suppress temperature sensitivity of cohesin complex mutants. Pds5p is SUMO conjugated, with sumoylation peaking during mitosis. SMT4 overexpression reduces Pds5p sumoylation, whereas smt4 mutants have increased Pds5p sumoylation. smt4 mutants were previously shown to be defective in cohesion maintenance during mitosis. These data provide the first link between a protein required for cohesion, Pds5p, and sumoylation, and suggest that Pds5p sumoylation promotes the dissolution of cohesion.

scholarly journals Saccharomyces cerevisiae DNA Polymerase ε and Polymerase σ Interact Physically and Functionally, Suggesting a Role for Polymerase ε in Sister Chromatid Cohesion

2003 ◽  
Vol 23 (8) ◽  
pp. 2733-2748 ◽  
Author(s):  
Shaune Edwards ◽  
Caroline M. Li ◽  
Daniel L. Levy ◽  
Jessica Brown ◽  
Peter M. Snow ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Polymerase ◽  
Sister Chromatid ◽  
Large Subunit ◽  
Polymerase Activity ◽  
Sister Chromatid Cohesion ◽  
Nucleotidyl Transferase ◽  
C Terminus ◽  
Chromatid Cohesion ◽  
A Subunit

ABSTRACT The large subunit of Saccharomyces cerevisiae DNA polymerase ε, Pol2, comprises two essential functions. The N terminus has essential DNA polymerase activity. The C terminus is also essential, but its function is unknown. We report here that the C-terminal domain of Pol2 interacts with polymerase σ (Pol σ), a recently identified, essential nuclear nucleotidyl transferase encoded by two redundant genes, TRF4 and TRF5. This interaction is functional, since Pol σ stimulates the polymerase activity of the Pol ε holoenzyme significantly. Since Trf4 is required for sister chromatid cohesion as well as for completion of S phase and repair, the interaction suggested that Pol ε, like Pol σ, might form a link between the replication apparatus and sister chromatid cohesion and/or repair machinery. We present evidence that pol2 mutants are defective in sister chromatid cohesion. In addition, Pol2 interacts with SMC1, a subunit of the cohesin complex, and with ECO1/CTF7, required for establishing sister chromatid cohesion; and pol2 mutations act synergistically with smc1 and scc1. We also show that trf5Δ mutants, like trf4Δ mutants, are defective in DNA repair and sister chromatid cohesion.

scholarly journals Hardwired synthetic lethality within the cohesin complex in human cancer cells

2017 ◽  
Author(s):  
Petra van der Lelij ◽  
Simone Lieb ◽  
Julian Jude ◽  
Gordana Wutz ◽  
Catarina P. Santos ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Cohesin Complex ◽  
Wild Type ◽  
Synthetic Lethal ◽  
Recurrent Mutations ◽  
Wide Range ◽  
Chromatid Cohesion

AbstractRecent genome analyses have identified recurrent mutations in the cohesin complex in a wide range of human cancers. Here we demonstrate that the most frequently mutated subunit of the cohesin complex, STAG2, displays a strong synthetic lethal interaction with its paralog STAG1. Mechanistically, STAG1 loss abrogates sister chromatid cohesion in STAG2 mutated but not in wild-type cells leading to mitotic catastrophe, defective cell division and apoptosis. STAG1 inactivation inhibits the proliferation of STAG2 mutated but not wild-type bladder cancer and Ewing sarcoma cell lines. Restoration of STAG2 expression in a mutated bladder cancer model alleviates the dependency on STAG1. Thus, STAG1 and STAG2 act redundantly to support sister chromatid cohesion and cell survival. STAG1 represents a hardwired, context independent vulnerability of cancer cells carrying mutations in the major emerging tumor suppressor STAG2. Exploiting synthetic lethal interactions to target recurrent cohesin mutations in cancer, e.g. by inhibiting STAG1, holds the promise for the development of selective therapeutics.

scholarly journals Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse cancer contexts

2017 ◽  
Author(s):  
Petra van der Lelij ◽  
Simone Lieb ◽  
Julian Jude ◽  
Gordana Wutz ◽  
Catarina P. Santos ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Sister Chromatid ◽  
Synthetic Lethality ◽  
Sister Chromatid Cohesion ◽  
Cohesin Complex ◽  
Wild Type ◽  
Synthetic Lethal ◽  
Recurrent Mutations ◽  
Wide Range ◽  
Chromatid Cohesion

AbstractRecent genome analyses have identified recurrent mutations in the cohesin complex in a wide range of human cancers. Here we demonstrate that the most frequently mutated subunit of the cohesin complex, STAG2, displays a strong synthetic lethal interaction with its paralog STAG1. Mechanistically, STAG1 loss abrogates sister chromatid cohesion in STAG2 mutated but not in wild-type cells leading to mitotic catastrophe, defective cell division and apoptosis. STAG1 inactivation inhibits the proliferation of STAG2 mutated but not wild-type bladder cancer and Ewing sarcoma cell lines. Restoration of STAG2 expression in a mutated bladder cancer model alleviates the dependency on STAG1. Thus, STAG1 and STAG2 support sister chromatid cohesion to redundantly ensure cell survival. STAG1 represents a vulnerability of cancer cells carrying mutations in the major emerging tumor suppressor STAG2 across different cancer contexts. Exploiting synthetic lethal interactions to target recurrent cohesin mutations in cancer, e.g. by inhibiting STAG1, holds the promise for the development of selective therapeutics.

scholarly journals Multivalent interaction of ESCO2 with the replication machinery is required for cohesion

2019 ◽  
Author(s):  
Dawn Bender ◽  
Eulália Maria Lima Da Silva ◽  
Jingrong Chen ◽  
Annelise Poss ◽  
Lauren Gawey ◽  
...  
Keyword(s):  
Cell Division ◽  
Dna Replication ◽  
Cohesin Complex ◽  
Replication Machinery ◽  
Replicative Helicase ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Mcm Helicase ◽  
N Terminus ◽  
Processivity Factor

AbstractThe tethering together of sister chromatids by the cohesin complex ensures their accurate alignment and segregation during cell division. In vertebrates, the establishment of cohesion between sister chromatids requires the activity of the ESCO2 acetyltransferase, which modifies the Smc3 subunit of cohesin. It was shown recently that ESCO2 promotes cohesion through interaction with the MCM replicative helicase. However, ESCO2 does not significantly colocalize with the MCM helicase, suggesting there may be additional interactions that are important for ESCO2 function. Here we show that ESCO2 is recruited to replication factories, the sites of DNA replication. We show that ESCO2 contains multiple conserved PCNA-interaction motifs in its N-terminus, and that each of these motifs are essential to ESCO2’s ability to establish sister chromatid cohesion. We propose that multiple PCNA interaction motifs embedded in a largely flexible and disordered region of the protein underlie the ability of ESCO2 to establish cohesion between sister chromatids precisely as they are born during DNA replication.SummaryCohesin modification by the ESCO2 acetyltransferase is required for cohesion between sister chromatids. Here we identify multiple motifs in ESCO2 that mediate its interaction with the replication processivity factor PCNA, and show that their mutation abrogates the ability of ESCO2 to ensure cohesion.

scholarly journals Biochemically distinct cohesin complexes mediate positioned loops between CTCF sites and dynamic loops within chromatin domains

2021 ◽  
Author(s):  
Yu Liu ◽  
Job Dekker
Keyword(s):  
Sister Chromatid ◽  
Structural Changes ◽  
Experimental Approach ◽  
Cohesin Complex ◽  
Genomic Context ◽  
Experimental Conditions ◽  
Chromatin Domains ◽  
Isolated Nuclei ◽  
Sister Chromatids ◽  
Chromatid Cohesion

The ring-like cohesin complex mediates sister chromatid cohesion by encircling pairs of sister chromatids. Cohesin also extrudes loops along chromatids. Whether the two activities involve similar mechanisms of DNA engagement is not known. We implemented an experimental approach based on isolated nuclei carrying engineered cleavable RAD21 proteins to precisely control cohesin ring integrity so that its role in chromatin looping could be studied under defined experimental conditions. This approach allowed us to identify cohesin complexes with distinct biochemical, and possibly structural properties, that mediate different sets of chromatin loops. When RAD21 is cleaved and the cohesin ring is opened, cohesin complexes at CTCF sites are released from DNA and loops at these elements are lost. In contrast, cohesin-dependent loops within chromatin domains and that are not anchored at CTCF sites are more resistant to RAD21 cleavage. The results show that the cohesin complex mediates loops in different ways depending on genomic context and suggests that it undergoes structural changes as it dynamically extrudes and encounters CTCF sites.

scholarly journals Cohesin recruits the Esco1 acetyltransferase genome wide to repress transcription and promote cohesion in somatic cells

2015 ◽  
Vol 112 (36) ◽  
pp. 11270-11275 ◽  
Author(s):  
Sadia Rahman ◽  
Mathew J. K. Jones ◽  
Prasad V. Jallepalli
Keyword(s):  
Cell Cycle ◽  
Gene Silencing ◽  
Sister Chromatid ◽  
Target Genes ◽  
Somatic Cells ◽  
S Phase ◽  
Cohesin Complex ◽  
Genome Wide ◽  
Chromatid Cohesion ◽  
Eukaryotic Genomes

The cohesin complex links DNA molecules and plays key roles in the organization, expression, repair, and segregation of eukaryotic genomes. In vertebrates the Esco1 and Esco2 acetyltransferases both modify cohesin’s Smc3 subunit to establish sister chromatid cohesion during S phase, but differ in their N-terminal domains and expression during development and across the cell cycle. Here we show that Esco1 and Esco2 also differ dramatically in their interaction with chromatin, as Esco1 is recruited by cohesin to over 11,000 sites, whereas Esco2 is infrequently enriched at REST/NRSF target genes. Esco1’s colocalization with cohesin occurs throughout the cell cycle and depends on two short motifs (the A-box and B-box) present in and unique to all Esco1 orthologs. Deleting either motif led to the derepression of Esco1-proximal genes and functional uncoupling of cohesion from Smc3 acetylation. In contrast, other mutations that preserved Esco1’s recruitment separated its roles in cohesion establishment and gene silencing. We conclude that Esco1 uses cohesin as both a substrate and a scaffold for coordinating multiple chromatin-based transactions in somatic cells.

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