Separase is a protease whose liberation from its inhibitory chaperone Securin triggers sister chromatid disjunction at anaphase onset in yeast by cleaving cohesins kleisin subunit. We have created conditional knockout alleles of the mouse Separase and Securin genes. Deletion of both copies of Separase but not Securin causes embryonic lethality. Loss of Securin reduces Separase activity because deletion of just one copy of the Separase gene is lethal to embryos lacking Securin. In embryonic fibroblasts, Separase depletion blocks sister chromatid separation but does not prevent other aspects of mitosis, cytokinesis, or chromosome replication. Thus, fibroblasts lacking Separase become highly polyploid. Hepatocytes stimulated to proliferate in vivo by hepatectomy also become unusually large and polyploid in the absence of Separase but are able to regenerate functional livers. Separase depletion in bone marrow causes aplasia and the presumed death of hematopoietic cells other than erythrocytes. Destruction

Now several years later we moved on and we found out that securin bound to this protein which we now called Separase and we didnt know…and Separase was required for the onset of anaphase. You could not separate sister chromatids without Separase. So we had this model that Separase bound securin. Like in that form it was inactive and the whole purpose of the anaphase promoting complex was to destroy the securin, liberate the Separase and then the Separase went off and did something magical to the chromosomes and maybe the spindle apparatus that would cause the sister chromatids to be pulled to opposite poles. And one of the big questions was what did Separase do, and it was really work that was done by a postdoc in my lab at the time a guy called Frank Uhlmann, who really cracked this problem. We had meanwhile identified many of the proteins that were directly involved in holding sister chromatids together. And again it was the discovery of the anaphase promoting complex and therefore the ...

Separase löst alle eukaryotischen Anaphasen aus, indem sie kohäsionsvermittelndes Cohesin spaltet. Bis dahin wird diese essentielle Protease durch Securin inhibiert. Separase kann alternativ durch Assoziation mit Cdk1-Cyclin B1 gehemmt werden, aber der entsprechende Komplex ist in der frühen Mitose wenig abundant und kann nicht erklären, warum Securin in Vertebraten entbehrlich ist. Die Proteinphosphatase 2A (PP2A) bindet Separase ebenfalls, aber die physiologische Rolle dieser Interaktion bleibt rätselhaft. Durch die Inaktivierung des spindle assembly checkpoint (SAC) in der Metaphase kann die Ubiquitin-Ligase APC/C die proteasomale Zerstörung von Securin (und Cyclin B1) vermitteln und dadurch Separase aktivieren. Obwohl sie strukturell mit Caspasen verwandt ist, wurde Separase bisher nicht mit der Apoptose in Verbindung gebracht. Stattdessen wurde in zwei Studien eine Rolle der Hefe-Separase bei der Reparatur von DNS-Schäden vorgeschlagen. Die Frage, ob diese nichtkanonische ...

Separase is a highly conserved cysteine protease required for proper chromosome segregation, and several other aspects of anaphase during both meiotic and mitotic stages of cell division (Peters et al. 2008). Separase proteolytic activity is inhibited during interphase and early mitosis by its pseudosubstrate inhibitor, securin (Nasmyth 2002). The protease activity of separase is critical for the cleavage of kleisin subunits of the cohesin complex (Uhlmann et al. 2000; Hauf et al. 2001). Cohesin holds sister chromatids together prior to their proper attachment to spindles and alignment on the metaphase plate preceding anaphase (Nasmyth and Haering 2009). Separase has also been implicated in various cell cycle regulatory functions. In budding yeast, separase stabilizes the anaphase spindle by cleaving the spindle and kinetochore-associated protein Slk19 (Sullivan et al. 2001). It is also involved in the release of the essential mitotic phosphatase Cdc14 in budding yeast (Sullivan and Uhlmann ...

The protease separase plays a key role in sister chromatid disjunction and centriole disengagement. To maintain genomic stability, separase activity is strictly regulated by binding of an inhibitory protein, securin. Despite its central role in cell division, the separase and securin complex is poorly understood at the structural level. This is partly owing to the difficulty of generating a sufficient quantity of homogeneous, stable protein. Here, we report the production of Caenorhabditis elegans separase-securin complex, and its characterization using biochemical methods and by negative staining electron microscopy. Single particle analysis generated a density map at a resolution of 21-24 Å that reveals a close, globular structure of complex connectivity harbouring two lobes. One lobe matches closely a homology model of the N-terminal HEAT repeat domain of separase, whereas the second lobe readily accommodates homology models of the separase C-terminal death and caspase-like domains. The ...

C. albicans is an important fungal pathogen of humans, and an understanding of the regulation of its cell cycle may reveal new targets for anti-fungal therapies. We previously characterized the C. albicans Anaphase Promoting Complex/Cyclosome regulatory co-factors Cdc20p and Cdh1p, and showed that they are important for the metaphase-to-anaphase transition and mitotic exit. In order to determine the mechanisms of action of Cdc20p, we searched the genome for factors that bind it in other systems, and found that C. albicans lacks the conserved Cdc20p target, securin. Securins bind and prevent separase from cleaving cohesin, and must be targeted for degradation by Cdc20p for separase-dependent sister chromatid separation. We hypothesized that C. albicans contains a divergent securin, which may be uncovered by identifying proteins that bind separase. We demonstrated that the C. albicans separase homologue, ESP1, is required for chromosome segregation. We then identified Esp1p-interacting factors ...

Separase Separase is a protein that is a cornerstone of cell division. Serperase is also known as Separin or Esp1. It allows for replicated chromosomes to be separated from their sister chromatids and pulled to opposite poles of the cell by the mitotic spindle, allowing for microfilaments to dissect the cell in half causing two genetically identical daughter cells from the single mother cell in mitosis or some haploid cells in Meiosis. The sister chromatids are held together by a protein called Cohesin, Separase catalyses and breaksdown cohesin allowing the sister chromatids to break apart, which in turn allows the mitotic spindle to draw the chromatids to either sides of the cell. Separase is crucial to the cell division process, not only does it physically separate the sister chromatids, it triggers the start of the anaphase period of cell division. Separase causes the cell to replicate accurately and on some occasions cause some problems if the protein is present or absent in excess ...

Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinsons disease, on cell motility. A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parsons lab at Kings College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinsons. Read more on her story here. Where could your research take you? The deadline to apply for the current round of Travelling Fellowships is 23rd Feburary 2018. Apply now!. ...

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Separase, A Caspase-like Cysteine Protease; Promotes Sister Chromatid Separation By Mediating Dissociation Of The Cohesin Scc1p From Chromatin; Inhibits Protein Phosphatase 2A-Cdc55p To Promote Mitotic Exit; Inhibited By Pds1p; Relative Distribution To The Nucleus Increases Upon DNA Replication Stress

Genomic instability develops in a wide variety of tumors, such as colon, breast, prostate, or lung cancers, as well as in adult T-cell leukemia (4, 29, 37, 38). For genetic damage to emerge and become sustained, multiple discrete events in a normal cell need to be disrupted. Dysregulated cellular functions involving centrosome amplification, silencing of checkpoints, and progression of the cell cycle have all been described to contribute to cellular transformation (29, 50). In published reports, HTLV-1 Tax has been shown to promote genomic instability through impairment of these various processes (22, 25, 27, 35, 47).. A tightly regulated separase activity is critical for proper chromosome segregation. Separase triggers partitioning of sister chromatids and influences mitotic spindle stability and mitotic exit (55, 56). PTTG/securin is a physiological inhibitor of separase, and aberrant PTTG function can alter the mechanics of chromosome segregation and create aneuploidy (52). Previously, it was ...

Background: In budding yeast, the protein phosphatase Cdc14 coordinates late mitotic events and triggers exit from mitosis. During early anaphase, Cdc14 is activated by the FEAR network, but how signaling through the FEAR network occurs is poorly understood. Results: We find that the FEAR network component Spo12 is phosphorylated on S118. This phosphorylation is essential for Spo12 function and is restricted to early anaphase, when the FEAR network is active. The anaphase-specific phosphorylation of Spo12 requires mitotic CDKs and depends on the FEAR network components Separase and Slk19. Furthermore, we find that CDC14 is required to maintain Spo12 in the dephosphorylated state prior to anaphase. Conclusions: Our results show that anaphase-specific phosphorylation of Spo12 is essential for FEAR network function and raise the interesting possibility that Cdc14 itself helps to prevent the FEAR network from being prematurely activated ...

Although the two-step removal systems in mitosis and meiosis are distinct, a common protein complex is implicated in protecting centromeric cohesion during the first step in both cases. Shugoshin/MEI-S332 family proteins collaborate with the phosphatase PP2A to prevent cohesin removal at centromeres [2], [4]. In mitosis, shugoshin-PP2A complexes antagonize SA phosphorylation by mitotic kinases, preventing removal by the prophase pathway (Figure 1A). In meiosis, shugoshin-PP2A antagonizes phosphorylation of Rec8, preventing cleavage by separase (Figure 1B) [2], [4]. A key question has been: What subsequently allows centromeric cohesion to be cleaved by separase in the second step? One proposed model is that, in response to tension across bi-oriented sister kinetochores, shugoshin-PP2A complexes move away from cohesin complexes at inner centromeres, making cohesin susceptible to removal by separase [5], [6]. Newly published studies, described below, propose two additional (related) mechanisms that ...

The Expression and Location of Survivin and Securin Proteins in a Variety of Human Cancer Cells. To examine the expression and location of securin and separase proteins relative to survivin protein in human cancer cells, the cells were subjected to immunoblot and immunofluorescence staining. As shown in Fig. 7A, a variety of human cancer cell lines including lung cancer (A549 and H1299) and colon cancer (RKO and SW480) expressed high levels of survivin and securin proteins. Moreover, we found that the securin-contained HCT116 cells but not the securin-null cells expressed the securin proteins (Fig. 7A). In these cell lines, the p53 proteins were expressed in the A549, RKO, SW480, and HCT116 cells but not H1299 cells (Fig. 7A). However, it has been shown that SW480 cells contained a G-to-A mutation in codon 273 and a C-to-T mutation in codon 309 of the p53 gene (Rodrigues et al., 1990; Weiss et al., 1993). The survivin proteins were expressed in all of the above cell lines, but the p53-mutated ...

Michelle Edwards and her nine-year-old daughter Alexis stepped into a hair salon for the first time in more than three years. Michelle has donated her hair 7 or 8 times since 2000.

ESP1-pRSG is an integrative plasmid carrying the ESP1 open reading frame in addition to 200 bases of the 5′ flanking sequence under the control of the GAL1 promoter. ESP1GFP-pRSG is derived from this plasmid by inserting a PCR-generated sequence encoding the GFP epitope (F64L, S65T, Q80R mutant) into a SmaI site introduced just before the stop codon. All pRSG-derived plasmids are linearized with StuI and integrants isolated by selecting for growth on dex-ura media. The parental pRSG plasmid is a derivative of pRS406 (Sikorski and Hieter 1989), where the NaeI-PvuI fragment spanning the multiple cloning site (MCS) linker has been substituted by the NaeI-PvuI fragment from pYES2 (Invitrogen) containing a MCS and the GAL1 promoter.. The ESP1myc18-pTRP1 plasmid was used to tag endogenous Esp1 protein with 18 myc epitopes at the COOH terminus. The integrative pTRP1 plasmid carries the sequence encoding six myc epitopes, which can be fused to a protein of interest at the NotI site (Mondesert et al. ...

Defining the mechanisms of chromosomal cohesion and dissolution of the cohesin complex from chromatids is important for understanding the chromosomal missegregation seen in many tumor cells. Here we report the identification of a novel cohesin-resolving protease and describe its role in chromosomal …

Wu, S.; Scheible, W.-R.; Schindelasch, D.; van Den Daele, H.; de Veylder, L.; Baskin, T. I.: A conditional mutation in Arabidopsis thaliana separase induces chromosome non-disjunction, aberrant morphogenesis and cyclin B1;1 stability. Development 137 (6), pp. 953 - 961 (2010 ...

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Recent years have witnessed remarkable strides in our understanding of the control of cell cycle progression. It is now clear that cell cycle progression is driven by the successive activation and inactivation of the Cdks, and that abrupt transitions are often enforced by the cleavage of key targets by the proteasome after their ubiquitination by various E3 ubiquitin ligases (for review see Murray, 2004). Cdk phosphorylation of key components regulates the entry of cells into S phase and choreographs the subsequent firing of replication origins. Entry into mitosis is also determined by Cdks, and Cdk phosphorylation of the nuclear lamins drives the cycle of nuclear envelope disassembly and reassembly that is characteristic of mitosis in metazoa. The exit from mitosis is triggered not only by proteolysis of mitotic cyclins but also of securin leading to the activation of separase, a CD clan protease that cleaves the rad21/Scc1 non-structural maintenance of chromosomes cohesin subunit, thereby ...

According to research from the University of Minnesota once the fear pathways are ramped up, the brain short-circuits more rational processing paths and reacts immediately to signals from the amygdala. When in this over-reactive state, the brain perceives events as negative and remembers them that way.. Fear affects memory, perception of reality and your health. Therefore, when we are faced with so many messages of fear, we are constantly processing large amounts of negative information, which affects our psyche. People can develop anxiety, depression, fatigue and even Post-traumatic stress disorder (PTSD). The good news is that if we train ourselves, we can beat fear.. How to stop fear We should try and make positive connections to the things that scare us most. We should take time to control our response to fear, so that we are not overridden with anxiety and stress every time we expect something negative to happen. In addition, perhaps we should pay less attention to the messages of fear we ...

Extensive biochemical and molecular analyses have shown that BubR1 plays a central role in spindle checkpoint activation (5 , 15 , 16) . It both coordinates the interaction of Bub3, Mad1, Mad2, and CENP-E with kinetochores and contributes to inhibition of APC activity during activation of this checkpoint. The APC is an E3 ubiquitin ligase that mediates the polyubiquitination of securin, thereby targeting it for degradation by the proteosome (16) . Securin binds to and inhibits the proteolytic activity of separase, which destroys the link between sister chromatids by cleaving the chromatid cohesin factor Scc1. Degradation of securin is required for the separation of sister chromatids during mitosis. Reduced levels of securin in BubR1+/− MEFs are closely correlated with BubR1 deficiency as well as with its activation status (Fig. 1C) ⇓ . Moreover, down-regulation of BubR1 via RNA interference resulted in almost complete disappearance of securin (Fig. 1D) ⇓ , strongly suggesting that BubR1 ...

Services Project is offering three different webinars on the engineering design process.. On Aug. 26 and Sept. 9, you can participate in the online seminar The Engineering Design Process: Part 1- Ask, Imagine, Plan. According to the AESP site, participants learn about problem identification, brainstorming and design challenges using the Spaghetti Anyone? tower building activity.. On Aug. 29, Part 2 - Create, Experiment, Improve will be offered. In this hands-on webinar, you will learn about the build, test and evaluate, redesign, and share-the-solution steps of the engineering design process.. On Sept. 23, you will learn how to modify your lessons to teach the engineering process in the session entitled Applying the Engineering Design Process to STEM Content.. AESP education specialists facilitate these free NASA webinars. You will not need any special software or equipment to participate. Simply go to the meeting room website listed on the AESP Webinar site to participate. To join the ...

Services Project is offering three different webinars on the engineering design process.. On Aug. 26 and Sept. 9, you can participate in the online seminar The Engineering Design Process: Part 1- Ask, Imagine, Plan. According to the AESP site, participants learn about problem identification, brainstorming and design challenges using the Spaghetti Anyone? tower building activity.. On Aug. 29, Part 2 - Create, Experiment, Improve will be offered. In this hands-on webinar, you will learn about the build, test and evaluate, redesign, and share-the-solution steps of the engineering design process.. On Sept. 23, you will learn how to modify your lessons to teach the engineering process in the session entitled Applying the Engineering Design Process to STEM Content.. AESP education specialists facilitate these free NASA webinars. You will not need any special software or equipment to participate. Simply go to the meeting room website listed on the AESP Webinar site to participate. To join the ...

Ada yang penggemar ESP? Istimewa pada semua penggemar ESP Shaklee, sebab bulan Januari 2019 ini, Shaklee menawarkan offer (promosi) menarik untuk pembelian ESP. Jadi, bolehlah anda semua grab offer ni cepat dan boleh buat bekalan selama berbulan-bulan. Sangat jimat dan menguntungkan sebab offer ESP ni memang jarang-jarang ada tau. Beli 7 Botol, Tapi Bayar 6 Botol Aje! Haa. Ini serius tau, bukan main-main. Kalau anda ingin mendapatkan 7 botol ESP untuk bekalan hampir 6-12 bulan, anda boleh terus grab offer Buy 7@6. Sebab, anda hanya perlu bayar untuk 6 botol sahaja. Bahasa lainnya beli 6 botol dapatlah extra lagi 1 botol ESP. Berbaloi kan? Istimewanya lagi bila anda beli set…. ...

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Cohesin is a highly conserved multisubunit complex that holds sister chromatids together in mitotic cells. At the metaphase to anaphase transition, proteolytic cleavage of the α kleisin subunit (Rad21) by separase causes cohesins dissociation from chromosomes and triggers sister-chromatid disjunction. To investigate cohesins function in postmitotic cells, where it is widely expressed, we have created fruit flies whose Rad21 can be cleaved by TEV protease. Cleavage causes precocious separation of sister chromatids and massive chromosome missegregation in proliferating cells, but not disaggregation of polytene chromosomes in salivary glands. Crucially, cleavage in postmitotic neurons is lethal. In mushroom-body neurons, it causes defects in axon pruning, whereas in cholinergic neurons it causes highly abnormal larval locomotion. These data demonstrate essential roles for cohesin in nondividing cells and also introduce a powerful tool by which to investigate protein function in metazoa. © 2008 Elsevier

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HDAC inhibitors are a promising class of anticancer agents (Bolden et al., 2006; Johnstone and Licht, 2003; Yoshida et al., 2003). However, our understanding of how HDAC inhibitors act within cells and why different cell types respond in different ways is limited. We employed the fission yeast S. pombe as a model, because this organism is sensitive to HDAC inhibitors and contains a set of HDAC genes similar to those of mammalian organisms. In the present study, we focused on the mitotic functions of three TSA-sensitive HDACs in fission yeast. Our results suggest that Clr6 negatively regulates APC/C independently of the PKA pathway and Mad2. By contrast, Mis4, the cohesin loader, is positively controlled by HDACs. HDAC inhibitors thus reduce the level of Mis4 and facilitate the exit from mitosis via the assembly of APC/C complex, leading to the direction of sister chromatid separation in dividing cells (Fig. 7D).. Given the known anti-proliferation effects of HDAC inhibitors on tumour cells, our ...

Chromosome segregation, transcriptional regulation, and repair of DNA double-strand breaks require the cohesin protein complex. Cohesin holds the replicated chromosomes (sister chromatids) together to mediate sister chromatid cohesion. The mechanism of how cohesion is established is unknown. We found that in budding yeast, the head domain of the Smc3p subunit of cohesin is acetylated by the Eco1p acetyltransferase at two evolutionarily conserved residues, promoting the chromatin-bound cohesin to tether sister chromatids. Smc3p acetylation is induced in S phase after the chromatin loading of cohesin and is suppressed in G1 and G2/M. Smc3 head acetylation and its cell cycle regulation provide important insights into the biology and mechanism of cohesion establishment. ...

Sister chromatid cohesion and homologue pairing at prometaphase I in solo; +, +; snm, and solo; snm mutants. X and Y chromosomes were recognized by probes again

The Elg1 Clamp Loader Plays a Role in Sister Chromatid Cohesion. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

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ESP: What it is and How to Develop it, Example, Evidence & Proof. ESP is always operating above and below normal consciousness. Click here to learn more.

So, terjawablah soalan-soalan basic tentang ESP ni..kepada anda yang berminat boleh hubungi saya ditalian 012-2541296 atau email ke [email protected] untuk mengetahui dengan lebih lanjut tentang produk ini..Oh ya! Promosi ESP ni sehingga 31st July, 2011 yea..! cepat dapatkannya sebagai persediaan berpuasa ...

My adventure with a zero-point-turn mower and the leadership and engagement ahas that ensued. Disengagement is a huge topic in business as 70% of...

Recently a test board for the ESP8266 ESP-12 arrived. I ordered it on AliExpress and took several weeks to arrive. Since the description was really

Thats what I thought. Another unevidenced claim by skeptics. You should be familiar with that kind of thing, its all you have.

Although the molecular function of PDS5 is still under investigation, several organisms require diverse function of PDS5 for chromatid cohesion (Losada et al., 2005). For example, it may act as a regulator of the SMC ATPase through the HEAT motifs shared by SCC2 (Kimura and Hirano, 2000) and thereby modulate the dynamics of the cohesin ring. Alternatively, PDS5 may act as a scaffolding protein and promote protein-protein interactions between adjacent cohesin complexes (Losada et al., 2005). An examination of the chromosomes from Pds5B-deficient mouse cells did not show any abnormalities in sister chromatid cohesion (i.e. PSCS). This result was in contrast to those obtained in budding yeast, worm and Drosophila, where PDS5 plays an important role in chromosome segregation (Dorsett et al., 2005; Hartman et al., 2000; Wang et al., 2003). It is possible that our assay in which a total of 50 cells were examined may not have detected subtle defects. Indeed, only mild cohesion defects were found in ...

Losada, A., Hirano, M., Hirano, T. (December 2002) Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis. Genes & Development, 16 (23). pp. 3004-3016. ISSN 0890-9369 Losada, A., Hirano, M., Hirano, T. (July 1998) Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. Genes and Development , 12 (13). pp. 1986-97. ISSN 0890-9369 (Print) Losada, A., Hirano, T. (February 2001) Intermolecular DNA interactions stimulated by the cohesin complex in vitro: Implications for sister chromatid cohesion. Current Biology, 11 (4). pp. 268-272. ISSN 0960-9822 Losada, A., Yokochi, T., Hirano, T. (May 2005) Functional contribution of Pds5 to cohesin-mediated cohesion in human cells and Xenopus egg extracts. J Cell Sci, 118 (Pt 10). pp. 2133-41. ISSN 0021-9533 (Print) ...

MAHSKTRTNDGKITYPPGVKEISDKISKEEMVRRLKMVVKTFMDMDQDSEEEKELYLNLALHLASDFFLK 1 - 70 HPDKDVRLLVACCLADIFRIYAPEAPYTSPDKLKDIFMFITRQLKGLEDTKSPQFNRYFYLLENIAWVKS 71 - 140 YNICFELEDSNEIFTQLYRTLFSVINNGHNQKVHMHMVDLMSSIICEGDTVSQELLDTVLVNLVPAHKNL 141 - 210 NKQAYDLAKALLKRTAQAIEPYITNFFNQVLMLGKTSISDLSEHVFDLILELYNIDSHLLLSVLPQLEFK 211 - 280 LKSNDNEERLQVVKLLAKMFGAKDSELASQNKPLWQCYLGRFNDIHVPIRLECVKFASHCLMNHPDLAKD 281 - 350 LTEYLKVRSHDPEEAIRHDVIVSIVTAAKKDILLVNDHLLNFVRERTLDKRWRVRKEAMMGLAQIYKKYA 351 - 420 LQSAAGKDAAKQIAWIKDKLLHIYYQNSIDDRLLVERIFAQYMVPHNLETTERMKCLYYLYATLDLNAVK 421 - 490 ALNEMWKCQNLLRHQVKDLLDLIKQPKTDASVKAIFSKVMVITRNLPDPGKAQDFMKKFTQVLEDDEKIR 491 - 560 KQLEVLVSPTCSCKQAEGCVREITKKLGNPKQPTNPFLEMIKFLLERIAPVHIDTESISALIKQVNKSID 561 - 630 GTADDEDEGVPTDQAIRAGLELLKVLSFTHPISFHSAETFESLLACLKMDDEKVAEAALQIFKNTGSKIE 631 - 700 EDFPHIRSALLPVLHHKSKKGPPRQAKYAIHCIHAIFSSKETQFAQIFEPLHKSLDPSNLEHLITPLVTI 701 - 770 GHIALLAPDQFAAPLKSLVATFIVKDLLMNDRLPGKKTTKLWVPDEEVSPETMVKIQAIKMMVRWLLGMK 771 - 840 ...

comment: Note that this term and its children should be used to annotate gene products found in cohesin complexes in organisms that undergo closed mitosis (i.e. where the nuclear envelope does not break down, as in fungi). For organisms in which the nuclear envelope breaks down during mitosis, the parent should be used ...

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TY - JOUR. T1 - Phosphorylation-enabled binding of SGO1-PP2A to cohesin protects sororin and centromeric cohesion during mitosis. AU - Liu, Hong. AU - Rankin, Susannah. AU - Yu, Hongtao. PY - 2013/1. Y1 - 2013/1. N2 - Timely dissolution of sister-chromatid cohesion in mitosis ensures accurate chromosome segregation to guard against aneuploidy and tumorigenesis. The complex of shugoshin and protein phosphatase 2A (SGO1-PP2A) protects cohesin at centromeres from premature removal by mitotic kinases and WAPL in prophase. Here we address the regulation and mechanism of human SGO1 in centromeric cohesion protection, and show that cyclin-dependent kinase (CDK)-mediated, mitosis-specific phosphorylation of SGO1 activates its cohesion-protection function and enables its direct binding to cohesin. The phospho-SGO1-bound cohesin complex contains PP2A, PDS5 and hypophosphorylated sororin, but lacks WAPL. Expression of non-phosphorylatable sororin bypasses the requirement for SGO1-PP2A in centromeric ...

Calpains form a family of Ca(2+)-dependent cysteine proteases involved in diverse cellular processes. However, the specific functions of each calpain isoform remain unknown. Recent reports have shown that calpain 2 (Capn2) is essential for cell viability. We have recently shown that Capn2 is a nuclear protease associated with chromosomes during mitosis in mammalian embryonic cells. We now report that Capn2 depletion impairs mitosis and induces apoptosis in murine cells. Low Capn2 levels induce chromosome alignment defects, the loss of histone H3 threonine 3 phosphorylation at centromeres, and premature sister chromatid separation. Thus, Capn2 may play a role in fundamental mitotic functions, such as the maintenance of sister chromatid cohesion.

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Molecular Biology Sci Aug 4, 00 Pol : A DNA Polymerase Required for Sister Chromatid Cohesion Zhenghe Wang, Irene B. Castaño,* Alejandro De Las Peñas,* Carrie Adams, Michael F. Christman Establishment of cohesion between sister chromatids is coupled to replication fork passage through an unknown mechanism. Here we report that TRF4, an evolutionarily conserved gene necessary for chromosome segregation, encodes a DNA polymerase with -polymerase-like properties. A double mutant in the redundant homologs, TRF4 and TRF5, is unable to complete S phase, whereas a trf4 single mutant completes a presumably defective S phase that results in a failure of cohesion between the replicated sister chromatids. This suggests that TRFs are a key link in the coordination between DNA replication and sister chromatid cohesion. Trf4 and Trf5 represent the fourth class of essential nuclear DNA polymerases (designated DNA polymerase kappa) in Saccharomyces cerevisiae and probably in all eukaryotes. Department of ...

Regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. May couple sister chromatid cohesion during mitosis to DNA replication. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. Plays a role in androgen-induced proliferative arrest in prostate cells.

The present study evaluated the dynamics and regulatory mechanisms of single cohesin molecules. We found that Scc2‐Scc4‐dependent topological loading and cohesin ATPase activity (disengagement of the head domain) are crucial for cohesin translocation along DNA. Consistent with this finding, the ATPase‐dependent translocation of cohesin in budding yeast was described in a previous study (Hu et al, 2011). Although Wapl‐Pds5 promotes the dissociation of cohesin from DNA as previously described (Gandhi et al, 2006; Kueng et al, 2006) (Appendix Fig S2C), we showed that Wapl‐Pds5 renders DNA‐associated cohesin immobile (Fig 2A and B). Considering that the engagement of Smc head domains restrains cohesin movement (Fig 1F), Wapl‐Pds5 may contribute to the tightening of the cohesin ring by associating with SA1, Scc1, and/or Smc3 (Shintomi & Hirano, 2009; Hara et al, 2014; Murayama & Uhlmann, 2015; Ouyang et al, 2016). Therefore, Wapl‐Pds5 may have dual activities: anti‐establishment ...

Premise (1) is true. Conclusion (3) sounds false. There are a couple of things that one can do about this odd argument. One can embrace the conclusion but insist that the conditional is only used materially, and is trivially true because the antecedent is false. One can-and I think this is going to be the most common reaction among philosophers-reject the inference of (3) from (2). But a lot of ordinary people will balk at (2)-the disjunction introduction step, where from p, we conclude p or q for any q.. Denying disjunction introduction neatly undercuts the above argument, as well as removing the oddity that everything can be proved from a contradiction.. But blocking disjunction introduction is a mistake, because we need disjunction introduction. Suppose that we say ...

I moved from a Subaru STI to the SLK55, and while the SLK is a hair faster/quicker, I find that its less stable at speeds above about 130mph. The car feels...