scholarly journals The Role of Cdc55 in the Spindle Checkpoint Is through Regulation of Mitotic Exit in Saccharomyces cerevisiae

2006 ◽  
Vol 17 (2) ◽  
pp. 658-666 ◽  
Author(s):  
Christopher M. Yellman ◽  
Daniel J. Burke
Keyword(s):  
Sister Chromatid ◽  
Spindle Checkpoint ◽  
Sister Chromatid Cohesion ◽  
Mitotic Exit ◽  
Negative Regulator ◽  
Regulatory Subunit ◽  
Checkpoint Activation ◽  
Chromatid Cohesion ◽  
Phosphatase 2A

Cdc55, a B-type regulatory subunit of protein phosphatase 2A, has been implicated in mitotic spindle checkpoint activity and maintenance of sister chromatid cohesion during metaphase. The spindle checkpoint is composed of two independent pathways, one leading to inhibition of the metaphase-to-anaphase transition by checkpoint proteins, including Mad2, and the other to inhibition of mitotic exit by Bub2. We show that Cdc55 is a negative regulator of mitotic exit. A cdc55 mutant, like a bub2 mutant, prematurely releases Cdc14 phosphatase from the nucleolus during spindle checkpoint activation, and premature exit from mitosis indirectly leads to loss of sister chromatid cohesion and inviability in nocodazole. The role of Cdc55 is separable from Bub2 and inhibits release of Cdc14 through a mechanism independent of the known negative regulators of mitotic exit. Epistasis experiments indicate Cdc55 acts either downstream or independent of the mitotic exit network kinase Cdc15. Interestingly, the B-type cyclin Clb2 is partially stable during premature activation of mitotic exit in a cdc55 mutant, indicating mitotic exit is incomplete.

scholarly journals Phosphatase 2A Negatively Regulates Mitotic Exit in Saccharomyces cerevisiae

2006 ◽  
Vol 17 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Yanchang Wang ◽  
Tuen-Yung Ng
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mitotic Exit ◽  
Regulatory Subunit ◽  
Temperature Sensitive ◽  
Cyclin Dependent Kinase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Catalytic Subunits ◽  
Phosphatase 2A ◽  
Negative Role

In budding yeast Saccharomyces cerevisiae, Cdc5 kinase is a component of mitotic exit network (MEN), which inactivates cyclin-dependent kinase (CDK) after chromosome segregation. cdc5-1 mutants arrest at telophase at the nonpermissive temperature due to the failure of CDK inactivation. To identify more negative regulators of MEN, we carried out a genetic screen for genes that are toxic to cdc5-1 mutants when overexpressed. Genes that encode the B-regulatory subunit (Cdc55) and the three catalytic subunits (Pph21, Pph22, and Pph3) of phosphatase 2A (PP2A) were isolated. In addition to cdc5-1, overexpression of CDC55, PPH21, or PPH22 is also toxic to other temperature-sensitive mutants that display defects in mitotic exit. Consistently, deletion of CDC55 partially suppresses the temperature sensitivity of these mutants. Moreover, in the presence of spindle damage, PP2A mutants display nuclear localized Cdc14, the key player in MEN pathway, indicative of MEN activation. All the evidence suggests the negative role of PP2A in mitotic exit. Finally, our genetic and biochemical data suggest that PP2A regulates the phosphorylation of Tem1, which acts at the very top of MEN pathway.

scholarly journals Saccharomyces cerevisiae CTF18 and CTF4 Are Required for Sister Chromatid Cohesion

2001 ◽  
Vol 21 (9) ◽  
pp. 3144-3158 ◽  
Author(s):  
Joseph S. Hanna ◽  
Evgueny S. Kroll ◽  
Victoria Lundblad ◽  
Forrest A. Spencer
Keyword(s):  
Sister Chromatid ◽  
Replication Fork ◽  
Spindle Assembly Checkpoint ◽  
Budding Yeast ◽  
Sister Chromatid Cohesion ◽  
Nuclear Antigen ◽  
Chromatid Cohesion ◽  
Core Components ◽  
Proliferating Cell

ABSTRACT CTF4 and CTF18 are required for high-fidelity chromosome segregation. Both exhibit genetic and physical ties to replication fork constituents. We find that absence of eitherCTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint. The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion. We find that Ctf18p, anRFC1-like protein, directly interacts with Rfc2p, Rfc3p, Rfc4p, and Rfc5p. However, Ctf18p is not a component of biochemically purified proliferating cell nuclear antigen loading RF-C, suggesting the presence of a discrete complex containing Ctf18p, Rfc2p, Rfc3p, Rfc4p, and Rfc5p. Recent identification and characterization of the budding yeast polymerase κ, encoded by TRF4, strongly supports a hypothesis that the DNA replication machinery is required for proper sister chromatid cohesion. Analogous to the polymerase switching role of the bacterial and human RF-C complexes, we propose that budding yeast RF-CCTF18 may be involved in a polymerase switch event that facilities sister chromatid cohesion. The requirement for CTF4 and CTF18 in robust cohesion identifies novel roles for replication accessory proteins in this process.

scholarly journals Protein phosphatase 2A regulates MPF activity and sister chromatid cohesion in budding yeast

1996 ◽  
Vol 6 (12) ◽  
pp. 1609-1620 ◽  
Author(s):  
Jeremy Minshull ◽  
Aaron Straight ◽  
Adam D. Rudner ◽  
Abby F. Dernburg ◽  
Andrew Belmont ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Protein Phosphatase ◽  
Budding Yeast ◽  
Protein Phosphatase 2A ◽  
Sister Chromatid Cohesion ◽  
Chromatid Cohesion ◽  
Phosphatase 2A

Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I

Nature ◽  
2006 ◽  
Vol 441 (7089) ◽  
pp. 53-61 ◽  
Author(s):  
Christian G. Riedel ◽  
Vittorio L. Katis ◽  
Yuki Katou ◽  
Saori Mori ◽  
Takehiko Itoh ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Sister Chromatid Cohesion ◽  
Chromatid Cohesion ◽  
Phosphatase 2A ◽  
Meiosis I

Sister chromatid cohesion and genome stability in vertebrate cells

2003 ◽  
Vol 31 (1) ◽  
pp. 263-265 ◽  
Author(s):  
C. Morrison ◽  
P. Vagnarelli ◽  
E. Sonoda ◽  
S. Takeda ◽  
W.C. Earnshaw
Keyword(s):  
Dna Repair ◽  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Genome Stability ◽  
Sister Chromatid Cohesion ◽  
Spindle Poles ◽  
Chromatid Cohesion ◽  
Chromosomal Passenger ◽  
Passenger Protein

For successful eukaryotic mitosis, sister chromatid pairs remain linked after replication until their kinetochores have been attached to opposite spindle poles by microtubules. This linkage is broken at the metaphase–anaphase transition and the sisters separate. In budding yeast, this sister chromatid cohesion requires a multi-protein complex called cohesin. A key component of cohesin is Scc1/Mcd1 (Rad21 in fission yeast). Disruption of the chicken orthologue of Scc1 by gene targeting in DT40 cells causes premature sister chromatid separation. Cohesion between sister chromatids is likely to provide a substrate for post-replicative DNA repair by homologous recombination. In keeping with this role of cohesion, Scc1 mutants also show defects in the repair of spontaneous and induced DNA damage. Scc1-deficient cells frequently fail to complete metaphase chromosome alignment and show chromosome segregation defects, suggesting aberrant kinetochore function. Consistent with this, the chromosomal passenger protein, INCENP (inner centromere protein) fails to localize to centromeres. Survivin, another passenger protein and one which interacts with INCENP, also fails to localize to centromeres in Scc1-deficient cells. These results show that cohesin maintains genomic stability by ensuring appropriate DNA repair and equal chromosome segregation at mitosis.

scholarly journals Mrc1 Is Required for Sister Chromatid Cohesion To Aid in Recombination Repair of Spontaneous Damage

2004 ◽  
Vol 24 (16) ◽  
pp. 7082-7090 ◽  
Author(s):  
Hong Xu ◽  
Charles Boone ◽  
Hannah L. Klein
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Homologous Recombination ◽  
Sister Chromatid ◽  
Synthetic Lethality ◽  
Dna Helicase ◽  
Sister Chromatid Cohesion ◽  
Checkpoint Response ◽  
Chromatid Cohesion

ABSTRACT The SRS2 gene of Saccharomyces cerevisiae encoding a 3′→5′ DNA helicase is part of the postreplication repair pathway and functions to ensure proper repair of DNA damage arising during DNA replication through pathways that do not involve homologous recombination. Through a synthetic gene array analysis, genes that are essential when Srs2 is absent have been identified. Among these are MRC1, TOF1, and CSM3, which mediate the intra-S checkpoint response. srs2Δ mrc1Δ synthetic lethality is due to inappropriate recombination, as the lethality can be suppressed by genetic elimination of homologous recombination. srs2Δ mrc1Δ synthetic lethality is dependent on the role of Mrc1 in DNA replication but independent of the role of Mrc1 in a DNA damage checkpoint response. mrc1Δ, tof1Δ and csm3Δ mutants have sister chromatid cohesion defects, implicating sister chromatid cohesion established at the replication fork as an important factor in promoting repair of stalled replication forks through gap repair.

scholarly journals Role of the DDX11 DNA Helicase in Warsaw Breakage Syndrome Etiology

2021 ◽  
Vol 22 (5) ◽  
pp. 2308
Author(s):  
Diana Santos ◽  
Mohammad Mahtab ◽  
Ana Boavida ◽  
Francesca M. Pisani
Keyword(s):  
Sister Chromatid ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Dna Helicase ◽  
Sister Chromatid Cohesion ◽  
Functional Coupling ◽  
Chromosome Loss ◽  
Loop Formation ◽  
Chromatid Cohesion

Warsaw breakage syndrome (WABS) is a genetic disorder characterized by sister chromatid cohesion defects, growth retardation, microcephaly, hearing loss and other variable clinical manifestations. WABS is due to biallelic mutations of the gene coding for the super-family 2 DNA helicase DDX11/ChlR1, orthologous to the yeast chromosome loss protein 1 (Chl1). WABS is classified in the group of “cohesinopathies”, rare hereditary diseases that are caused by mutations in genes coding for subunits of the cohesin complex or protein factors having regulatory roles in the sister chromatid cohesion process. In fact, among the cohesion regulators, an important player is DDX11, which is believed to be important for the functional coupling of DNA synthesis and cohesion establishment at the replication forks. Here, we will review what is known about the molecular and cellular functions of human DDX11 and its role in WABS etiopathogenesis, even in light of recent findings on the role of cohesin and its regulator network in promoting chromatin loop formation and regulating chromatin spatial organization.

scholarly journals Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Pedro Ortega ◽  
Belén Gómez-González ◽  
Andrés Aguilera
Keyword(s):  
Sister Chromatid ◽  
Histone Deacetylases ◽  
Genome Stability ◽  
Genome Instability ◽  
Sister Chromatid Cohesion ◽  
Histone Deacetylation ◽  
Strand Breaks ◽  
Chromatid Cohesion ◽  
Dna Strands

AbstractGenome stability involves accurate replication and DNA repair. Broken replication forks, such as those encountering a nick, lead to double strand breaks (DSBs), which are preferentially repaired by sister-chromatid recombination (SCR). To decipher the role of chromatin in eukaryotic DSB repair, here we analyze a collection of yeast chromatin-modifying mutants using a previously developed system for the molecular analysis of repair of replication-born DSBs by SCR based on a mini-HO site. We confirm the candidates through FLP-based systems based on a mutated version of the FLP flipase that causes nicks on either the leading or lagging DNA strands. We demonstrate that Rpd3L and Hda1 histone deacetylase (HDAC) complexes contribute to the repair of replication-born DSBs by facilitating cohesin loading, with no effect on other types of homology-dependent repair, thus preventing genome instability. We conclude that histone deacetylation favors general sister chromatid cohesion as a necessary step in SCR.

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