Separase is a caspase-like cysteine protease, which plays a central role in triggering ANAPHASE by cleaving the SCC1/RAD21 subunit of the cohesin complex. Cohesin holds the sister CHROMATIDS together during METAPHASE and its cleavage results in chromosome segregation.
Securin is involved in the control of the metaphase-anaphase transition during MITOSIS. It promotes the onset of anaphase by blocking SEPARASE function and preventing proteolysis of cohesin and separation of sister CHROMATIDS. Overexpression of securin is associated with NEOPLASTIC CELL TRANSFORMATION and tumor formation.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
Either of the two longitudinally adjacent threads formed when a eukaryotic chromosome replicates prior to mitosis. The chromatids are held together at the centromere. Sister chromatids are derived from the same chromosome. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.
A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.
An order of fungi in the phylum Ascomycota that multiply by budding. They include the telomorphic ascomycetous yeasts which are found in a very wide range of habitats.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.
The process by which the CYTOPLASM of a cell is divided.

Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. (1/153)

A vertebrate securin (vSecurin) was identified on the basis of its biochemical analogy to the Pds1p protein of budding yeast and the Cut2p protein of fission yeast. The vSecurin protein bound to a vertebrate homolog of yeast separins Esp1p and Cut1p and was degraded by proteolysis mediated by an anaphase-promoting complex in a manner dependent on a destruction motif. Furthermore, expression of a stable Xenopus securin mutant protein blocked sister-chromatid separation but did not block the embryonic cell cycle. The vSecurin proteins share extensive sequence similarity with each other but show no sequence similarity to either of their yeast counterparts. Human securin is identical to the product of the gene called pituitary tumor-transforming gene (PTTG), which is overexpressed in some tumors and exhibits transforming activity in NIH 3T3 cells. The oncogenic nature of increased expression of vSecurin may result from chromosome gain or loss, produced by errors in chromatid separation.  (+info)

Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. (2/153)

In eukaryotic cells, replicated DNA strands remain physically connected until their segregation to opposite poles of the cell during anaphase. This "sister chromatid cohesion" is essential for the alignment of chromosomes on the mitotic spindle during metaphase. Cohesion depends on the multisubunit cohesin complex, which possibly forms the physical bridges connecting sisters. Proteolytic cleavage of cohesin's Sccl subunit at the metaphase to anaphase transition is essential for sister chromatid separation and depends on a conserved protein called separin. We show here that separin is a cysteine protease related to caspases that alone can cleave Sccl in vitro. Cleavage of Sccl in metaphase arrested cells is sufficient to trigger the separation of sister chromatids and their segregation to opposite cell poles.  (+info)

Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separin. (3/153)

It has been proposed but never proven that cohesion between sister chromatids distal to chiasmata is responsible for holding homologous chromosomes together while spindles attempt to pull them toward opposite poles during metaphase of meiosis I. Meanwhile, the mechanism by which disjunction of homologs is triggered at the onset of anaphase I has remained a complete mystery. In yeast, cohesion between sister chromatid arms during meiosis depends on a meiosis-specific cohesin subunit called Rec8, whose mitotic equivalent, Sccl, is cleaved at the metaphase to anaphase transition by an endopeptidase called separin. We show here that cleavage of Rec8 by separin at one of two different sites is necessary for the resolution of chiasmata and the disjunction of homologous chromosomes during meiosis.  (+info)

Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase. (4/153)

In yeast, anaphase depends on cohesin cleavage. How anaphase is controlled in vertebrates is unknown because their cohesins dissociate from chromosomes before anaphase. We show that residual amounts of the cohesin SCC1 remain associated with human centromeres until the onset of anaphase when a similarly small amount of SCC1 is cleaved. In Xenopus extracts, SCC1 cleavage depends on the anaphase-promoting complex and separin. Separin immunoprecipitates are sufficient to cleave SCC1, indicating that separin is associated with a protease activity. Separin activation coincides with securin destruction and partial separin cleavage, suggesting that several mechanisms regulate separin activity. We propose that in vertebrates, a cleavage-independent pathway removes cohesin from chromosome arms during prophase, whereas a separin-dependent pathway cleaves centromeric cohesin at the metaphase-anaphase transition.  (+info)

A novel role of the budding yeast separin Esp1 in anaphase spindle elongation: evidence that proper spindle association of Esp1 is regulated by Pds1. (5/153)

In Saccharomyces cerevisiae, the metaphase-anaphase transition is initiated by the anaphase-promoting complex-dependent degradation of Pds1, whereby Esp1 is activated to promote sister chromatid separation. Although this is a fundamental step in the cell cycle, little is known about the regulation of Esp1 and how loss of cohesion is coordinated with movement of the anaphase spindle. Here, we show that Esp1 has a novel role in promoting anaphase spindle elongation. The localization of Esp1 to the spindle apparatus, analyzed by live cell imaging, is regulated in a manner consistent with a function during anaphase B. The protein accumulates in the nucleus in G2 and is mobilized onto the spindle pole bodies and spindle midzone at anaphase onset, where it persists into midanaphase. Association with Pds1 occurs during S phase and is required for efficient nuclear targeting of Esp1. Spindle association is not fully restored in pds1 mutants expressing an Esp1-nuclear localization sequence fusion protein, suggesting that Pds1 is also required to promote Esp1 spindle binding. In agreement, Pds1 interacts with the spindle at the metaphase-anaphase transition and a fraction remains at the spindle pole bodies and the spindle midzone in anaphase cells. Finally, mutational analysis reveals that the conserved COOH-terminal region of Esp1 is important for spindle interaction.  (+info)

Cohesin cleavage by separase required for anaphase and cytokinesis in human cells. (6/153)

Cell division depends on the separation of sister chromatids in anaphase. In yeast, sister separation is initiated by cleavage of cohesin by the protease separase. In vertebrates, most cohesin is removed from chromosome arms by a cleavage-independent mechanism. Only residual amounts of cohesin are cleaved at the onset of anaphase, coinciding with its disappearance from centromeres. We have identified two separase cleavage sites in the human cohesin subunit SCC1 and have conditionally expressed noncleavable SCC1 mutants in human cells. Our results indicate that cohesin cleavage by separase is essential for sister chromatid separation and for the completion of cytokinesis.  (+info)

Orchestrating anaphase and mitotic exit: separase cleavage and localization of Slk19. (7/153)

Anaphase in budding yeast is triggered by cleavage of the central subunit, Scc1, of the chromosomal cohesin complex by the protease separase. Here we show that separase also cleaves the kinetochore-associated protein Slk19 at anaphase onset. Separase activity is also required for the proper localization of a stable Slk19 cleavage product to the spindle midzone in anaphase. The cleavage and localization of Slk19 are necessary to stabilize the anaphase spindle, and we show that a stable spindle is a prerequisite for timely exit from mitosis. This demonstrates the cleavage of targets other than cohesin by separase in the orchestration of high-fidelity anaphase.  (+info)

Drosophila separase is required for sister chromatid separation and binds to PIM and THR. (8/153)

Drosophila PIM and THR are required for sister chromatid separation in mitosis and associate in vivo. Neither of these two proteins shares significant sequence similarity with known proteins. However, PIM has functional similarities with securin proteins. Like securin, PIM is degraded at the metaphase-to-anaphase transition and this degradation is required for sister chromatid separation. Securin binds and inhibits separase, a conserved cysteine endoprotease. Proteolysis of securin at the metaphase-to-anaphase transition activates separase, which degrades a conserved cohesin subunit, thereby allowing sister chromatid separation. To address whether PIM regulates separase activity or functions with THR in a distinct pathway, we have characterized a Drosophila separase homolog (SSE). SSE is an unusual member of the separase family. SSE is only about one-third the size of other separases and has a diverged endoprotease domain. However, our genetic analyses show that SSE is essential and required for sister chromatid separation during mitosis. Moreover, we show that SSE associates with both PIM and THR. Although our work shows that separase is required for sister chromatid separation in higher eukaryotes, in addition, it also indicates that the regulatory proteins have diverged to a surprising degree, particularly in Drosophila.  (+info)

Separase is not a medical term itself, but it is a biological term used in the field of cell biology and genetics. Separase is an enzyme that plays a crucial role in the separation of chromosomes during cell division (mitosis and meiosis).

In more detail, separase is a protease enzyme that contributes to the breakdown of cohesin complexes, which are protein structures that hold sister chromatids together after DNA replication. Separase's function is essential for the proper separation of chromosomes during anaphase, the stage of mitosis where sister chromatids are pulled apart and moved to opposite poles of the cell.

While not a medical term per se, understanding separase and its role in cell division can help researchers better understand certain genetic disorders or diseases that may be caused by errors in cell division.

Securin is not a medical term, but rather a biological concept related to cell division. It's a protein that plays a crucial role in the regulation of chromosome separation during cell division (mitosis).

During mitosis, sister chromatids (identical copies of a chromosome) are held together by cohesin proteins until it's time for them to separate and move to opposite ends of the cell. Securin is one of the proteins that helps regulate this process. Specifically, securin inhibits an enzyme called separase, which is responsible for cleaving the cohesin rings that hold sister chromatids together.

Once the cell is ready to separate its chromosomes, a protease called separase is activated and degrades securin. This allows separase to cleave the cohesin rings, leading to the separation of sister chromatids and the continuation of mitosis. If securin function is disrupted, it can lead to errors in chromosome segregation, which can contribute to genomic instability and diseases like cancer.

Endopeptidases are a type of enzyme that breaks down proteins by cleaving peptide bonds inside the polypeptide chain. They are also known as proteinases or endoproteinases. These enzymes work within the interior of the protein molecule, cutting it at specific points along its length, as opposed to exopeptidases, which remove individual amino acids from the ends of the protein chain.

Endopeptidases play a crucial role in various biological processes, such as digestion, blood coagulation, and programmed cell death (apoptosis). They are classified based on their catalytic mechanism and the structure of their active site. Some examples of endopeptidase families include serine proteases, cysteine proteases, aspartic proteases, and metalloproteases.

It is important to note that while endopeptidases are essential for normal physiological functions, they can also contribute to disease processes when their activity is unregulated or misdirected. For instance, excessive endopeptidase activity has been implicated in the pathogenesis of neurodegenerative disorders, cancer, and inflammatory conditions.

Chromatids are defined as the individual strands that make up a duplicated chromosome. They are formed during the S phase of the cell cycle, when replication occurs and each chromosome is copied, resulting in two identical sister chromatids. These chromatids are connected at a region called the centromere and are held together by cohesin protein complexes until they are separated during mitosis or meiosis.

During mitosis, the sister chromatids are pulled apart by the mitotic spindle apparatus and distributed equally to each daughter cell. In meiosis, which is a type of cell division that occurs in the production of gametes (sex cells), homologous chromosomes pair up and exchange genetic material through a process called crossing over. After crossing over, each homologous chromosome consists of two recombinant chromatids that are separated during meiosis I, and then sister chromatids are separated during meiosis II.

Chromatids play an essential role in the faithful transmission of genetic information from one generation to the next, ensuring that each daughter cell or gamete receives a complete set of chromosomes with intact and functional genes.

Anaphase is a stage in the cell division process called mitosis, where sister chromatids (the two copies of each chromosome formed during DNA replication) separate at the centromeres and move toward opposite poles of the cell. This separation is facilitated by the attachment of microtubules from the spindle apparatus to the kinetochores, protein structures located on the centromeres of each sister chromatid. Anaphase is followed by telophase, during which the nuclear membrane reforms around each set of separated chromosomes, and cytokinesis, the division of the cytoplasm to form two separate daughter cells.

Chromosome segregation is the process that occurs during cell division (mitosis or meiosis) where replicated chromosomes are separated and distributed equally into two daughter cells. Each chromosome consists of two sister chromatids, which are identical copies of genetic material. During chromosome segregation, these sister chromatids are pulled apart by a structure called the mitotic spindle and moved to opposite poles of the cell. This ensures that each new cell receives one copy of each chromosome, preserving the correct number and composition of chromosomes in the organism.

Cell cycle proteins are a group of regulatory proteins that control the progression of the cell cycle, which is the series of events that take place in a eukaryotic cell leading to its division and duplication. These proteins can be classified into several categories based on their functions during different stages of the cell cycle.

The major groups of cell cycle proteins include:

1. Cyclin-dependent kinases (CDKs): CDKs are serine/threonine protein kinases that regulate key transitions in the cell cycle. They require binding to a regulatory subunit called cyclin to become active. Different CDK-cyclin complexes are activated at different stages of the cell cycle.
2. Cyclins: Cyclins are a family of regulatory proteins that bind and activate CDKs. Their levels fluctuate throughout the cell cycle, with specific cyclins expressed during particular phases. For example, cyclin D is important for the G1 to S phase transition, while cyclin B is required for the G2 to M phase transition.
3. CDK inhibitors (CKIs): CKIs are regulatory proteins that bind to and inhibit CDKs, thereby preventing their activation. CKIs can be divided into two main families: the INK4 family and the Cip/Kip family. INK4 family members specifically inhibit CDK4 and CDK6, while Cip/Kip family members inhibit a broader range of CDKs.
4. Anaphase-promoting complex/cyclosome (APC/C): APC/C is an E3 ubiquitin ligase that targets specific proteins for degradation by the 26S proteasome. During the cell cycle, APC/C regulates the metaphase to anaphase transition and the exit from mitosis by targeting securin and cyclin B for degradation.
5. Other regulatory proteins: Several other proteins play crucial roles in regulating the cell cycle, such as p53, a transcription factor that responds to DNA damage and arrests the cell cycle, and the polo-like kinases (PLKs), which are involved in various aspects of mitosis.

Overall, cell cycle proteins work together to ensure the proper progression of the cell cycle, maintain genomic stability, and prevent uncontrolled cell growth, which can lead to cancer.

Chromosomal proteins, non-histone, are a diverse group of proteins that are associated with chromatin, the complex of DNA and histone proteins, but do not have the characteristic structure of histones. These proteins play important roles in various nuclear processes such as DNA replication, transcription, repair, recombination, and chromosome condensation and segregation during cell division. They can be broadly classified into several categories based on their functions, including architectural proteins, enzymes, transcription factors, and structural proteins. Examples of non-histone chromosomal proteins include high mobility group (HMG) proteins, poly(ADP-ribose) polymerases (PARPs), and condensins.

Mitosis is a type of cell division in which the genetic material of a single cell, called the mother cell, is equally distributed into two identical daughter cells. It's a fundamental process that occurs in multicellular organisms for growth, maintenance, and repair, as well as in unicellular organisms for reproduction.

The process of mitosis can be broken down into several stages: prophase, prometaphase, metaphase, anaphase, and telophase. During prophase, the chromosomes condense and become visible, and the nuclear envelope breaks down. In prometaphase, the nuclear membrane is completely disassembled, and the mitotic spindle fibers attach to the chromosomes at their centromeres.

During metaphase, the chromosomes align at the metaphase plate, an imaginary line equidistant from the two spindle poles. In anaphase, sister chromatids are pulled apart by the spindle fibers and move toward opposite poles of the cell. Finally, in telophase, new nuclear envelopes form around each set of chromosomes, and the chromosomes decondense and become less visible.

Mitosis is followed by cytokinesis, a process that divides the cytoplasm of the mother cell into two separate daughter cells. The result of mitosis and cytokinesis is two genetically identical cells, each with the same number and kind of chromosomes as the original parent cell.

Metaphase is a phase in the cell division process (mitosis or meiosis) where the chromosomes align in the middle of the cell, also known as the metaphase plate or equatorial plane. During this stage, each chromosome consists of two sister chromatids attached to each other by a protein complex called the centromere. The spindle fibers from opposite poles of the cell attach to the centromeres of each chromosome, and through a process called congression, they align the chromosomes in the middle of the cell. This alignment allows for accurate segregation of genetic material during the subsequent anaphase stage.

Nuclear proteins are a category of proteins that are primarily found in the nucleus of a eukaryotic cell. They play crucial roles in various nuclear functions, such as DNA replication, transcription, repair, and RNA processing. This group includes structural proteins like lamins, which form the nuclear lamina, and regulatory proteins, such as histones and transcription factors, that are involved in gene expression. Nuclear localization signals (NLS) often help target these proteins to the nucleus by interacting with importin proteins during active transport across the nuclear membrane.

Protein Phosphatase 2 (PP2A) is a type of serine/threonine protein phosphatase that plays a crucial role in the regulation of various cellular processes, including signal transduction, cell cycle progression, and metabolism. PP2A is a heterotrimeric enzyme composed of a catalytic subunit (C), a regulatory subunit A (A), and a variable regulatory subunit B (B). The different combinations of the B subunits confer specificity to PP2A, allowing it to regulate a diverse array of cellular targets.

PP2A is responsible for dephosphorylating many proteins that have been previously phosphorylated by protein kinases. This function is essential for maintaining the balance of phosphorylation and dephosphorylation in cells, which is necessary for proper protein function and cell signaling. Dysregulation of PP2A has been implicated in various diseases, including cancer, neurodegenerative disorders, and cardiovascular disease.

Cyclin B1 is a type of cyclin protein that regulates the cell cycle, specifically the transition from G2 phase to mitosis (M phase) in eukaryotic cells. It forms a complex with and acts as a regulatory subunit of cyclin-dependent kinase 1 (CDK1), also known as CDC2. During the G2 phase, Cyclin B1 levels accumulate and upon reaching a certain threshold, it binds to CDK1 to form the maturation promoting factor (MPF). The activation of MPF triggers the onset of mitosis by promoting nuclear envelope breakdown, chromosome condensation, and other events required for cell division. After the completion of mitosis, Cyclin B1 is degraded by the ubiquitin-proteasome system, allowing the cell cycle to progress back into G1 phase.

A centromere is a specialized region found on chromosomes that plays a crucial role in the separation of replicated chromosomes during cell division. It is the point where the sister chromatids (the two copies of a chromosome formed during DNA replication) are joined together. The centromere contains highly repeated DNA sequences and proteins that form a complex structure known as the kinetochore, which serves as an attachment site for microtubules of the mitotic spindle during cell division.

During mitosis or meiosis, the kinetochore facilitates the movement of chromosomes by interacting with the microtubules, allowing for the accurate distribution of genetic material to the daughter cells. Centromeres can vary in their position and structure among different species, ranging from being located near the middle of the chromosome (metacentric) to being positioned closer to one end (acrocentric). The precise location and characteristics of centromeres are essential for proper chromosome segregation and maintenance of genomic stability.

Meiosis is a type of cell division that results in the formation of four daughter cells, each with half the number of chromosomes as the parent cell. It is a key process in sexual reproduction, where it generates gametes or sex cells (sperm and eggs).

The process of meiosis involves one round of DNA replication followed by two successive nuclear divisions, meiosis I and meiosis II. In meiosis I, homologous chromosomes pair, form chiasma and exchange genetic material through crossing over, then separate from each other. In meiosis II, sister chromatids separate, leading to the formation of four haploid cells. This process ensures genetic diversity in offspring by shuffling and recombining genetic information during the formation of gametes.

Saccharomycetales is an order of fungi that are commonly known as "true yeasts." They are characterized by their single-celled growth and ability to reproduce through budding or fission. These organisms are widely distributed in nature and can be found in a variety of environments, including soil, water, and on the surfaces of plants and animals.

Many species of Saccharomycetales are used in industrial processes, such as the production of bread, beer, and wine. They are also used in biotechnology to produce various enzymes, vaccines, and other products. Some species of Saccharomycetales can cause diseases in humans and animals, particularly in individuals with weakened immune systems. These infections, known as candidiasis or thrush, can affect various parts of the body, including the skin, mouth, and genital area.

Saccharomyces cerevisiae proteins are the proteins that are produced by the budding yeast, Saccharomyces cerevisiae. This organism is a single-celled eukaryote that has been widely used as a model organism in scientific research for many years due to its relatively simple genetic makeup and its similarity to higher eukaryotic cells.

The genome of Saccharomyces cerevisiae has been fully sequenced, and it is estimated to contain approximately 6,000 genes that encode proteins. These proteins play a wide variety of roles in the cell, including catalyzing metabolic reactions, regulating gene expression, maintaining the structure of the cell, and responding to environmental stimuli.

Many Saccharomyces cerevisiae proteins have human homologs and are involved in similar biological processes, making this organism a valuable tool for studying human disease. For example, many of the proteins involved in DNA replication, repair, and recombination in yeast have human counterparts that are associated with cancer and other diseases. By studying these proteins in yeast, researchers can gain insights into their function and regulation in humans, which may lead to new treatments for disease.

Cyclin B is a type of cyclin protein that regulates the cell cycle, specifically the transition from G2 phase to mitosis (M phase) in eukaryotic cells. Cyclin B binds and activates cyclin-dependent kinase 1 (CDK1), forming the complex known as M-phase promoting factor (MPF). This complex triggers the events leading to cell division, such as chromosome condensation, nuclear envelope breakdown, and spindle formation. The levels of cyclin B increase during the G2 phase and are degraded by the anaphase-promoting complex/cyclosome (APC/C) at the onset of anaphase, allowing the cell cycle to progress into the next phase.

Cytokinesis is the part of the cell division process (mitosis or meiosis) in which the cytoplasm of a single eukaryotic cell divides into two daughter cells. It usually begins after telophase, and it involves the constriction of a contractile ring composed of actin filaments and myosin motor proteins that forms at the equatorial plane of the cell. This results in the formation of a cleavage furrow, which deepens and eventually leads to the physical separation of the two daughter cells. Cytokinesis is essential for cell reproduction and growth in multicellular organisms, and its failure can lead to various developmental abnormalities or diseases.

Active separase can then cleave Scc1 for release of the sister chromatids. Separase initiates the activation of Cdc14 in early ... Note that separase cannot function without initially forming the securin-separase complex in most organisms. This is because ... the CDK1-cyclin B complex inhibits separase by rigidifying pseudosubstrate motifs from flexible loops in separase itself, ... In S. cerevisiae, separase is encoded by the esp1 gene. Esp1 was discovered by Kim Nasmyth and coworkers in 1998. In 2021, ...
Separase bound to securin remains inhibited; however, when inhibition is relieved, activated separase cleaves the cohesin ... Securin destruction liberates and activates its bound protease partner, separase. ...
During anaphase, cohesin is cleaved by separase. Topoisomerase II and condensin are responsible for removing catenations. The ... or separase. Meiotic nondisjunction has been well studied in Saccharomyces cerevisiae. This yeast undergoes mitosis similarly ...
Separase is vital for onset of anaphase. This securin-separase complex is maintained when securin is phosphorylated by Cdk1, ... When bound to securin, separase is not functional. In addition, both securin and separase are well-conserved proteins (Figure 1 ... Note that separase cannot function without initially forming the securin-separase complex. This is because securin helps ... rapid destruction of securin and activation of separase is vital for proper anaphase. Overall, securin and separase act in an ...
Securin releases separase, a protease, when degraded. Separase then triggers the cleavage of cohesin, the protein complex that ... When securin undergoes ubiquitination by the APC/C and releases separase, which degrades cohesin, sister chromatids become free ...
that separase activates Cdc14, which in turn acts on securin, thus creating a positive feedback loop that increases the ... Released and active separase cleaves cohesin that held sister chromatids together, facilitating separation of sister chromatids ... Matt Sullivan; Frank Uhlmann (2003). "A non-proteolytic function of separase links anaphase onset to mitotic exit". Nat Cell ... Their results indicate that interfering with this positive securin-separase-cdc14 loop decreases sister chromatid separation ...
Released and active separase cleaves cohesin that held sister chromatids together, facilitating separation of sister chromatids ... Matt Sullivan, Frank Uhlmann (2003). "A non-proteolytic function of separase links anaphase onset to mitotic exit". Nat Cell ... Peters (2002). "Regulation of Human Separase by Securin Binding and Autocleavage". Current Biology. 12 (16): 1368-1378. doi: ... the role of separase and Cdc14 endocycles". J. R. Soc. Interface. 8 (61): 1128-1141. doi:10.1098/rsif.2010.0649. PMC 3119881. ...
Waizenegger I, Giménez-Abián JF, Wernic D, Peters JM (Aug 2002). "Regulation of human separase by securin binding and ...
"AO FIM DE SEIS ANOS, SEPARA-SE DE TERESA CAEIRO". Nova Gente. Retrieved 19 June 2021. Portugal portal (Articles with short ...
Securin is a protein which inhibits a protease known as separase. The destruction of securin unleashes separase which then ... causes the APC to cleave the M-phase cyclin and the inhibitory protein securin which activates the separase protease to cleave ...
The ubiquitination and destruction of securin at the end of metaphase releases the active protease called separase. Separase ... Securin degradation releases the protease Esp1p/separase, which degrades the cohesin rings that link the two sister chromatids ... The multipolar metaphase-anaphase transition occurs through an incomplete separase cycle that results in frequent ... separin or separase). When anaphase onset is triggered, the anaphase-promoting complex (APC/C or Cyclosome) degrades securin. ...
Gorr IH, Boos D, Stemmann O (2005). "Mutual inhibition of separase and Cdk1 by two-step complex formation". Mol. Cell. 19 (1): ...
"Shugoshin-PP2A counteracts casein-kinase-1-dependent cleavage of Rec8 by separase". Nature Cell Biology. 12 (5): 500-6. doi: ... "Rec8 phosphorylation by casein kinase 1 and Cdc7-Dbf4 kinase regulates cohesin cleavage by separase during meiosis". ...
This includes a binding site for SA1 or SA2, recognition motifs for separase, caspase, and calpain to cleave, as well as a ... Hauf S, Waizenegger IC, Peters JM (August 2001). "Cohesin cleavage by separase required for anaphase and cytokinesis in human ... RAD21 is cleaved by several proteases including Separase and Calcium-dependent cysteine endopeptidase Calpain-1 during mitosis ... and its dissolution by the cysteine protease Separase at the metaphase to anaphase transition results in the separation of ...
"Canciller Mayta posesiona a nuevos viceministros con la misión de no separase del pueblo". comunicacion.gob.bo (in Spanish). 1 ...
At that point the mother and daughter centrioles separate dependently on an enzyme called separase. The two centrioles in the ...
... has been shown to interact with: calmodulin, separase, CEP215, CHD3/4, protein kinase A, protein kinase C, DISC1, γ- ... Lee K, Rhee K (Jul 2012). "Separase-dependent cleavage of pericentrin B is necessary and sufficient for centriole disengagement ...
... separase, PIKKs (phosphatidylinositol 3-kinase-related protein kinases) such as ATM (Ataxia telangiectasia mutated) and ATR ( ... "Cryo-EM structure of a metazoan separase-securin complex at near-atomic resolution". Nat Struct Mol Biol. 24 (4): 414-418. doi: ... "A closed conformation of the Caenorhabditis elegans separase-securin complex". Open Biol. 6 (4): 160032. doi: 10.1098/rsob. ... "Structure predictions and interaction studies indicate homology of separase N-terminal regulatory domains and Drosophila THR". ...
The latter is a protein whose function is to inhibit separase, which in turn cuts the cohesins, the protein composite ... Once this inhibitory protein is degraded via ubiquitination and subsequent proteolysis, separase then causes sister chromatid ...
The resulting destruction of securing release separase, which hydrolyzes cohesion - the protein that binds sister chromatids ...
The formation of these "inhibitory complexes" and steps feed into a 'wait' signal before activation of separase; at the stage ... prior to anaphase, securin inhibits the activity of separase and maintains the cohesion complex. The crystal structure of Bub3 ...
Sister chromatids require active separase to hydrolyze the cohesin that bind them together prior to progression to anaphase. ... As long as securin and cyclin B remain active, separase remains inactive, preventing premature progression to anaphase. The ...
The homologs are cleaved by the enzyme separase to release the cohesin that held the homologous chromosome arms together. This ...
Therefore, in order for anaphase to progress, securin must be inhibited so that cohesin can be cleaved by separase. These ... Securin is a protein that inhibits separase, which in turn inhibits cohesin, a protein that holds sister chromatids together. ...
"Division of the nucleolus and its release of CDC14 during anaphase of meiosis I depends on separase, SPO12, and SLK19". ...
This cohesion is later broken by the enzyme separase, allowing the chiasmata to be broken and homologous chromosomes to ... Age-related degeneration of the inhibitors and regulators of separase, may lead to inappropriate and premature cohesin ...
... remains in complex with SMC proteins until anaphase, where it is degraded by Separase once the spindle assembly checkpoint ... Bypass of the spindle assembly checkpoint activates Separase, which then degrades phosphorylated Rec8 and untethers Cohesin ...
... separase. This results in the sister chromatids remaining tethered. Shugoshin also acts as a spindle checkpoint component. It ...
This includes a binding site for SA1 or SA2, recognition motifs for separase cleavage and a region that is competitively bound ... Securin is cleaved at anaphase, following APC/C-cdc20 mediated degradation, and it renders separase (a protease, inhibited by ...
... that sister chromatids are held together within this ring and that they are released by cleavage of cohesin by separase. ...

No data available that match "separase"


  • In 2021, structures of human separase were determined in complex with either securin or CDK1-cyclin B1-CKS1 using cryo-EM by scientists of the University of Geneva. (wikipedia.org)
  • When the cell is not dividing, separase is prevented from cleaving cohesin through its association with either securin or upon phosphorylation of a specific serine residue in separase by the cyclin-CDK complex. (wikipedia.org)
  • However, while securin contains its own pseudosubstrate motifs to occlude substrate binding, the CDK1-cyclin B complex inhibits separase by rigidifying pseudosubstrate motifs from flexible loops in separase itself, leading to an auto-inhibition of the proteolytic activity of separase. (wikipedia.org)
  • Note that separase cannot function without initially forming the securin-separase complex in most organisms. (wikipedia.org)
  • This is because securin helps properly fold separase into the functional conformation. (wikipedia.org)
  • However, yeast does not appear to require securin to form functional separase because anaphase occurs in yeast even with a securin deletion. (wikipedia.org)
  • On the signal for anaphase, securin is ubiquitinated and hydrolysed, releasing separase for dephosphorylation by the APC-Cdc20 complex. (wikipedia.org)
  • Separase initiates the activation of Cdc14 in early anaphase and Cdc14 has been found to dephosphorylate securin, thereby increasing its efficiency as a substrate for degradation. (wikipedia.org)
  • Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin 1 . (nature.com)
  • SGO2-MAD2 can functionally replace securin and sequesters most separase in securin-knockout cells. (nature.com)
  • Acute loss of securin and SGO2, but not of either protein individually, resulted in separase deregulation associated with premature cohesin cleavage and cytotoxicity. (nature.com)
  • Thus, our results identify an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC. (nature.com)
  • Cryo-EM structure of a metazoan separase-securin complex at near-atomic resolution. (nature.com)
  • Separase can alternatively be inhibited by association with Cdk1-cyclin B1 but the corresponding complex is scarce in early mitosis and cannot explain why vertebrate securin is dispensable. (uni-bayreuth.de)
  • Silencing of the spindle assembly checkpoint (SAC) in metaphase enables the ubiquitin ligase APC/C to mediate the proteasomal destruction of securin (and cyclin B1), thereby activating separase. (uni-bayreuth.de)
  • 1) Securin associates co-translationally with separase and prevents its aggregation. (uni-bayreuth.de)
  • This suggests that it might assist the proper folding of this giant protease and offers a first mechanistic explanation for the genetic evidence that securin is not only an inhibitor but also an activator of separase. (uni-bayreuth.de)
  • While free securin is phosphorylated in mitosis, separase-bound securin is kept in an unphosphorylated state by associated PP2A. (uni-bayreuth.de)
  • This effecuates supernumerous securin to be degraded first and largely gone by the time separase-associated securin is targeted for proteolysis. (uni-bayreuth.de)
  • 3) Once liberated, separase is subject to conformational change by the peptidyl-prolyl isomerase Pin1 and thereby rendered resistant against residual securin. (uni-bayreuth.de)
  • 4) Pin1 catalyzed trans-to-cis isomerization of separase is essential for Cdk1-cyclin B1-dependent inhibition and explains why the kinase and securin bind separase in a mutually exclusive manner. (uni-bayreuth.de)
  • It is enabled by SAC-activated Mad2 to bind and inhibit separase and can functionally replace securin. (uni-bayreuth.de)
  • Acute depletion of Sgo2 and securin (but not the individual knock-downs) result in separase deregulation and premature loss of cohesion. (uni-bayreuth.de)
  • Thus, while the canonical, securin-dependent branch of anaphase control requires proteolysis, the release of active separase from Sgo2-Mad2 does not. (uni-bayreuth.de)
  • Separase proteolytic activity is tightly regulated by a number of inhibitory mechanisms combining Securin binding, JAK phosphorylation precise serine residue phosphorylation by CyclinB1 Cdk1, PP2A binding and autocatalytic cleavage. (pkc-inhibitors.com)
  • Securin degradation then unleashes separase to promote sister-chromatid separation. (biomedcentral.com)
  • Esp1 is a separase protein that cleaves the cohesin subunit Scc1 (RAD21), allowing sister chromatids to separate at the onset of anaphase during mitosis. (wikipedia.org)
  • Here, separase is activated and locally cleaves cohesin, which might grant the repair machinery access to the damaged DNA. (uni-bayreuth.de)
  • We show here that separase cleaves mouse Rec8 at three positions in vitro but only when the latter is hyper-phosphorylated. (ox.ac.uk)
  • Initiating the anaphase, a protein known as separase cleaves the cohesins, proteins that hold the sister chromatids together. (biologyideas.com)
  • The second step involves cleavage of the cohesin subunit SCC1 (RAD21) by separase, which initiates the final separation of sister chromatids. (wikipedia.org)
  • Separase universally triggers eukaryotic anaphases by cleavage of sister chromatid cohesion mediating cohesin. (uni-bayreuth.de)
  • 10) Cleavage of Mcl1 and Bcl-xL by separase transforms these pro-survival factors into proapoptotic fragments and triggers death in mitosis via the intrinsic pathway of apoptosis. (uni-bayreuth.de)
  • Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. (ox.ac.uk)
  • Separase, a cysteine endopeptidase, conducts cleavage of cohesin. (pkc-inhibitors.com)
  • It is known that the final trigger of centriole disengagement is cleavage by separase. (uni-bayreuth.de)
  • In early anaphase, upon separase downregulation of PP2A Cdc55 , Scc1 dephosphorylation is inhibited, promoting cohesin cleavage. (encyclopedia.pub)
  • ESPL1 / separase, a cysteine ​​endopeptidase, is a key player in centrosome duplication and mitotic sister chromatid separation. (separase.com)
  • For quantification of separase transcript amounts, the business Hs ESPL1 one SG QuantiTect Primer Assay was employed based on the instructions in the manufacturer. (wee1signaling.com)
  • Separase, also known as separin, is a cysteine protease responsible for triggering anaphase by hydrolysing cohesin, which is the protein responsible for binding sister chromatids during the early stage of anaphase. (wikipedia.org)
  • Thereby, premature activation of separase is prevented and the metaphase-to-anaphase transition sharpened. (uni-bayreuth.de)
  • Expression of Rec8-N in oocytes causes chromosome segregation to be asynchronous and delays its completion by 2-3 hours during anaphase I, probably due to inefficient proteolysis of Rec8-N by separase. (ox.ac.uk)
  • Accordingly, endogenous cyclin A is localized to kinetochores throughout meiosis II, but not in anaphase I. Additionally, we found that cyclin B1, but not cyclin A2, inhibits separase in meiosis I. These findings indicate that separase-dependent cohesin removal is differentially regulated by cyclin B1 and A2 in mammalian meiosis. (ox.ac.uk)
  • Separase is a caspase-like cysteine protease, which plays a central role in triggering ANAPHASE by cleaving the SCC1/RAD21 subunit of the cohesin complex. (bvsalud.org)
  • Cohesin disappeared from the centrosomes only upon activation of separase in anaphase, which correlated with the timing of centriole disengagement in late mitosis. (uni-bayreuth.de)
  • Ectopic activation of Separase proteolytic activity brings about premature sister chromatide separation and centriole disengagement. (pkc-inhibitors.com)
  • We observed a publish translational activation of Separase proteolytic activity in BCR ABL positive cells soon after treatment method with therapeutic IM doses. (pkc-inhibitors.com)
  • 6) Upon destruction of this last cyclin B1 in early G1 phase, separase is released from the late Cdk1-cyclin B1-separase complex and triggers centriole disengagement, thereby licensing later centrosome duplication. (uni-bayreuth.de)
  • Instead, two studies suggested a role of yeast separase in DNA damage repair but left unanswered whether this non-canonical interphase function of separase is conserved in mammals. (uni-bayreuth.de)
  • Rec8, the meiosis-specific alpha-kleisin subunit of cohesin, is a key target of separase in yeast. (ox.ac.uk)
  • Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast. (ginsim.org)
  • Proteolytic activity of separase is required for chiasma resolution during meiosis I in mouse oocytes. (ox.ac.uk)
  • We report on separase transcription, protein expression, and Separase proteolytic activity. (pkc-inhibitors.com)
  • Protein phosphatase 2A (PP2A) also binds separase but the physiological role of this interaction remains enigmatic. (uni-bayreuth.de)
  • Moreover, separase-dependent processing transforms MCL1 and BCL-XL from anti-apoptotic factors into pro-apoptotic protein fragments. (healthcare-in-europe.com)
  • We have now beforehand found a hyperlink between growth and a posh comprising the Arabidopsis caspase-like protease separase (additionally named EXTRA SPINDLE POLES [ESP]) and three Arabidopsis microtubule (MT)-based centromeric protein-E-like Kinesins 7 (KIN7), which belong to the so-called KIN7.3-clade (KIN7.1, KIN7.3, and KIN7.5). (keiseronlineuniversity.com)
  • In S. cerevisiae, separase is encoded by the esp1 gene. (wikipedia.org)
  • APC/C-dependent ubiquitylation and action of the AAA-ATPase TRIP13 in conjunction with the MAD2-specific adaptor p31 comet liberate separase from SGO2-MAD2 in vitro. (nature.com)
  • Fig. 4: TRIP13-p31 comet -dependent disassembly liberates separase from SGO2-MAD2. (nature.com)
  • 8) The AAA-ATPase Trip13 actively disassembles the separase-Sgo2-Mad2 complex upon SAC silencing in metaphase. (uni-bayreuth.de)
  • Cyclin A2 is required for sister chromatid segregation, but not separase control, in mouse oocyte meiosis. (ox.ac.uk)
  • Separase removes the cohesin complex holding sister chromatids together in a stepwise manner from chromosome arms in meiosis I, then from the centromere region in meiosis II. (ox.ac.uk)
  • namely, its requirement for separase-dependent sister chromatid separation in meiosis II. (ox.ac.uk)
  • Gorr IH, Reis A, Boos D, Wuhr M, Madgwick S, Jones KT, Stemmann O. Essential CDK1-inhibitory role for separase during meiosis I in vertebrate oocytes . (ncl.ac.uk)
  • Sepin-1 is a small compound that inhibits the enzymatic activity of Separase and growth of cancer cells. (separase.com)
  • Separase phosphorylation leads to a stable association with CDK1-cyclin B1. (wikipedia.org)
  • 5) Formation of the Cdk1-cyclin B1-separase complex is counter-acted by phosphorylation of cyclin B1 in early mitosis. (uni-bayreuth.de)
  • The absolute quantification strategy: application to phosphorylation profiling of human separase serine 1126. (kettenbachlab.org)
  • Here we show that human shugoshin 2 (SGO2), an essential protector of meiotic cohesin with unknown functions in the soma 6 , 7 , is turned into a separase inhibitor upon association with SAC-activated MAD2. (nature.com)
  • Fig. 3: SGO2 is a MAD2-dependent, competitive inhibitor of separase. (nature.com)
  • Stability and pharmacokinetics of separase inhibitor-sepin-1 in sprague-dawley rats. (separase.com)
  • The acquiring that separase is overexpressed in many cancers, including CML renders this protease a essential subject of investigation to unravel the molecular mechanisms involved with the growth of centrosome amplification in IM handled CML. (pkc-inhibitors.com)
  • Dephosphorylation results in a second peak of Cdk1-cyclin B1-separase complex formation in late mitosis when most cyclin B1 has already been degraded. (uni-bayreuth.de)
  • This happens because the separase re-purposes two proteins that usually have the task of counteracting apoptosis. (healthcare-in-europe.com)
  • Yet, when separase becomes active too early, it cuts these two proteins. (healthcare-in-europe.com)
  • It ensures that the separase spares healthy cells and actually only attacks the proteins MCL1 and BCL-XL in the case of an imminent pathological cell development. (healthcare-in-europe.com)
  • The separase is prepared for this attack as soon as the two proteins have been modified by phosphate groups. (healthcare-in-europe.com)
  • Active separase can then cleave Scc1 for release of the sister chromatids. (wikipedia.org)
  • La separasa es una proteasa de cisteína parecida a la caspasa, que juega un importante papel en el desencadenamiento de la ANAFASE mediante la escisión de la subunidad SCC1/RAD21 del complejo cohesina. (bvsalud.org)
  • Despite being structurally related to caspases, separase has not been previously linked to apoptosis. (uni-bayreuth.de)
  • It is the separase itself that prevents the threatening consequences of its premature activity: it induces the dividing cell to undergo suicide, a process known as apoptosis. (healthcare-in-europe.com)
  • A conditional mutation in Arabidopsis thaliana separase induces chromosome non-disjunction, aberrant morphogenesis and cyclin B1;1 stability. (mpg.de)
  • Overexpression of separase continues to be reported to induce aneuploidy and tumorigenesis. (pkc-inhibitors.com)
  • 11) Mcl1 and Bcl-xL are substrates for separase only when phosphorylated by Nek2a. (uni-bayreuth.de)
  • In this case, the separase fulfils its functions at the right time, without being able to identify and attack the no longer phosphorylated MCL1 and BCL-XL. (healthcare-in-europe.com)
  • Therefore, a promising approach in the fight against cancer could now be to encourage separase-dependent transformation of MCL1 and BCL-XL into pro-apoptotic factors because this would be especially harmful to diseased cells. (healthcare-in-europe.com)
  • Right: If the spindle assembly checkpoint is defective, the activities of NEK2A and separase timely overlap (purple area). (healthcare-in-europe.com)
  • However, if the spindle assembly checkpoint is defective, the process of cell division is accelerated: And while NEK2A is still present in the cell, the separase becomes active. (healthcare-in-europe.com)
  • 9) Human separase facilitates the repair of DNA double strand breaks (DSBs) by homologous recombination. (uni-bayreuth.de)
  • Un om con la fas roja sta con un vitro en la mano, e par sinias nonesata de mano atenta produi alga silentia. (elefen.org)
  • Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS. (separase.com)
  • Separase activity distribution can be a marker of major molecular response and proliferation of CD34+ cells in TKI-treated chronic myeloid leukemia patients. (separase.com)
  • Effects Study style and cell line characterization To analyze the conditional context in between p210BCR ABL, separase activity and IM remedy, we carried out cell culture experiments applying a panel of six nicely established human cell lines. (pkc-inhibitors.com)
  • If the separase is activated too early, there is a risk of cellular transformation into malignant cancer cells. (healthcare-in-europe.com)
  • Fig. 1: MAD2-dependent binding of human SGO2 to separase. (nature.com)
  • Synthetic peptide from human SEPARASE. (covalab.com)
  • Reacts with human Separase. (covalab.com)
  • In both complexes, separase is inhibited by pseudosubstrate motifs that block substrate binding at the catalytic site and at nearby docking sites. (wikipedia.org)