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Spindle Assembly Checkpoint

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https://www.readbyqxmd.com/read/28933982/function-and-regulation-mechanism-of-chk1-during-meiotic-maturation-in-porcine-oocytes
#1
Zheng-Wen Nie, Li Chen, Qiu-Shi Jin, Ying-Ying Gao, Tao Wang, Xia Zhang, Yi-Liang Miao
Checkpoint 1 (Chk1), as an important member of DNA replication checkpoint and DNA damage response, has an important role during the G2/M stage of mitosis. In this study, we used porcine oocyte as a model to investigate the function of Chk1 during porcine oocyte maturation. Chk1 was expressed from germinal vesicle (GV) to metaphase II (MII) stages, mainly localized in the cytoplasm at GV stage and moved to the spindle after germinal vesicle breakdown (GVBD). Chk1 depletion not only induced oocytes to be arrested at MI stage with abnormal chromosomes arrangement, but also inhibited the degradation of Cyclin B1 and decreased the expression of Mitotic Arrest Deficient 2-Like 1 (Mad2L1), one of spindle assembly checkpoint (SAC) proteins, and cadherin 1 (Cdh1), one of coactivation for anaphase-promoting complex/cyclosome (APC/C)...
September 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28928489/the-phosphorylation-of-a-kinetochore-protein-dam1-by-aurora-b-ipl1-kinase-promotes-chromosome-bipolar-attachment-in-yeast
#2
Fengzhi Jin, Michael Bokros, Yanchang Wang
The interaction between chromosomes and spindle microtubules is essential for chromosome segregation. The kinetochore complex mediates this interaction. Previous studies indicate that the stability of kinetochore attachment is regulated by Aurora B/Ipl1 kinase and this regulation is conserved from yeast to mammalian cells. In budding yeast Saccharomyces cerevisiae, the ten-subunit Dam1/DASH complex bridges the interaction between kinetochores and microtubules, and some in vitro evidence indicates that the phosphorylation of Dam1 protein by Ipl1 kinase destabilizes this interaction...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851945/delayed-apc-c-activation-extends-the-first-mitosis-of-mouse-embryos
#3
Anna Ajduk, Bernhard Strauss, Jonathon Pines, Magdalena Zernicka-Goetz
The correct temporal regulation of mitosis underpins genomic stability because it ensures the alignment of chromosomes on the mitotic spindle that is required for their proper segregation to the two daughter cells. Crucially, sister chromatid separation must be delayed until all the chromosomes have attached to the spindle; this is achieved by the Spindle Assembly Checkpoint (SAC) that inhibits the Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase. In many species the first embryonic M-phase is significantly prolonged compared to the subsequent divisions, but the reason behind this has remained unclear...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851706/dna-damage-induces-a-kinetochore-based-atm-atr-independent-sac-arrest-unique-to-the-first-meiotic-division-in-mouse-oocytes
#4
Simon I R Lane, Stephanie L Morgan, Tianyu Wu, Josie K Collins, Julie A Merriman, Elias ElInati, James M Turner, Keith T Jones
Mouse oocytes carrying DNA damage arrest in meiosis I, thereby preventing creation of embryos with deleterious mutations. The arrest is dependent on the spindle assembly checkpoint, which results in anaphase-promoting complex (APC) inhibition. However, little is understood about how this checkpoint is engaged following DNA damage. Here, we find that within minutes DNA damage assembles checkpoint proteins at the kinetochore, not at damage sites along chromosome arms, such that the APC is fully inhibited within 30 min...
August 29, 2017: Development
https://www.readbyqxmd.com/read/28840249/a-kinase-phosphatase-network-that-regulates-kinetochore-microtubule-attachments-and-the-sac
#5
Giulia Vallardi, Marilia Henriques Cordeiro, Adrian Thomas Saurin
The KMN network (for KNL1, MIS12 and NDC80 complexes) is a hub for signalling at the outer kinetochore. It integrates the activities of two kinases (MPS1 and Aurora B) and two phosphatases (PP1 and PP2A-B56) to regulate kinetochore-microtubule attachments and the spindle assembly checkpoint (SAC). We will first discuss each of these enzymes separately, to describe how they are regulated at kinetochores and why this is important for their primary function in controlling either microtubule attachments or the SAC...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28840248/molecular-mechanisms-of-spindle-assembly-checkpoint-activation-and-silencing
#6
Kevin D Corbett
In eukaryotic cell division, the Spindle Assembly Checkpoint (SAC) plays a key regulatory role by monitoring the status of chromosome-microtubule attachments and allowing chromosome segregation only after all chromosomes are properly attached to spindle microtubules. While the identities of SAC components have been known, in some cases, for over two decades, the molecular mechanisms of the SAC have remained mostly mysterious until very recently. In the past few years, advances in biochemical reconstitution, structural biology, and bioinformatics have fueled an explosion in the molecular understanding of the SAC...
2017: Progress in Molecular and Subcellular Biology
https://www.readbyqxmd.com/read/28829971/how-kinetochore-architecture-shapes-the%C3%A2-mechanisms-of-its-function
#7
REVIEW
Ajit P Joglekar, Alexander A Kukreja
The eukaryotic kinetochore is a sophisticated multi-protein machine that segregates chromosomes during cell division. To ensure accurate chromosome segregation, it performs three major functions using disparate molecular mechanisms. It operates a mechanosensitive signaling cascade known as the spindle assembly checkpoint (SAC) to detect and signal the lack of attachment to spindle microtubules, and delay anaphase onset in response. In addition, after attaching to spindle microtubules, the kinetochore generates the force necessary to move chromosomes...
August 21, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28821799/plk1-bound-to-bub1-contributes-to-spindle-assembly-checkpoint-activity-during-mitosis
#8
Masanori Ikeda, Kozo Tanaka
For faithful chromosome segregation, the formation of stable kinetochore-microtubule attachment and its monitoring by the spindle assembly checkpoint (SAC) are coordinately regulated by mechanisms that are currently ill-defined. Here, we show that polo-like kinase 1 (Plk1), which is instrumental in forming stable kinetochore-microtubule attachments, is also involved in the maintenance of SAC activity by binding to Bub1, but not by binding to CLASP2 or CLIP-170. The effect of Plk1 on the SAC was found to be mediated through phosphorylation of Mps1, an essential kinase for the SAC, as well as through phosphorylation of the MELT repeats in Knl1...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794013/control-mechanisms-in-germ-cells-mediated-by-p53-family-proteins
#9
REVIEW
Jakob Gebel, Marcel Tuppi, Katharina Krauskopf, Daniel Coutandin, Susanne Pitzius, Sebastian Kehrloesser, Christian Osterburg, Volker Dötsch
Germ cells are totipotent and, in principle, immortal as they are the source for new germ cells in each generation. This very special role requires tight quality control systems. The p53 protein family constitutes one of the most important quality surveillance systems in cells. Whereas p53 has become famous for its role as the guardian of the genome in its function as the most important somatic tumor suppressor, p63 has been nicknamed 'guardian of the female germ line'. p63 is strongly expressed in resting oocytes and responsible for eliminating those that carry DNA double-strand breaks...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28763871/-the-function-of-aurora-a-and-its-role-in-the-development-of-liver-cancer
#10
M Li, Z G Ren
Aurora A plays a key role in cellular mitosis. It is located in the centrosome and spindle, and is mainly involved in the processes of centrosome maturation and separation, bipolar spindle assembly, and the regulation of mitotic progression. Recent studies have suggested that Aurora A is involved in tumorigenesis and tumor development through multiple mechanisms. Overexpression of Aurora A could cause abnormal centrosome amplification, aneuploidy formation, and G2/M checkpoint defects, which result in chromosome instability and imbalance between cell division and apoptosis, and eventually leads to abnormal cell proliferation...
June 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28759042/inhibition-of-the-spindle-assembly-checkpoint-kinase-mps-1-as-a-novel-therapeutic-strategy-in-malignant-mesothelioma
#11
A Szymiczek, M Carbone, S Pastorino, A Napolitano, M Tanji, M Minaai, I Pagano, J M Mason, H I Pass, M R Bray, T W Mak, H Yang
Malignant mesothelioma (MM) is an aggressive malignancy, highly resistant to current medical and surgical therapies, whose tumor cells characteristically show a high level of aneuploidy and genomic instability. We tested our hypothesis that targeting chromosomal instability in MM would improve response to therapy. Thr/Tyr kinase (TTK)/monopolar spindle 1 kinase (Mps-1) is a kinase of the spindle assembly checkpoint that controls cell division and cell fate. CFI-402257 is a novel, selective inhibitor of Mps-1 with antineoplastic activity...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28757527/rad51-maintains-chromosome-integrity-and-mitochondrial-distribution-during-porcine-oocyte-maturation-in-vitro
#12
Zhe-Long Jin, Nam-Hyung Kim
DNA repair protein RAD51 homolog 1 (RAD51) plays a central role in homologous recombination (HR) repair of DNA breaks. HR depends on the formation of a RAD51 recombinase filament that facilitates strand invasion. However, the role of RAD51 during porcine oocyte maturation is unknown. The objective of this study was to investigate the expression and function of RAD51 during porcine oocyte maturation in vitro. RAD51 was mainly localized to the nucleus at the germinal vesicle (GV) stage, and was widely distributed in the cytoplasm between the GV breakdown (GVBD) and metaphase II stage...
July 30, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28754846/overexpression-of-the-e2f-target-gene-cenpi-promotes-chromosome-instability-and-predicts-poor-prognosis-in-estrogen-receptor-positive-breast-cancer
#13
Pulari U Thangavelu, Cheng-Yu Lin, Srividya Vaidyanathan, Thu H M Nguyen, Eloise Dray, Pascal H G Duijf
During cell division, chromosome segregation is facilitated by the mitotic checkpoint, or spindle assembly checkpoint (SAC), which ensures correct kinetochore-microtubule attachments and prevents premature sister-chromatid separation. It is well established that misexpression of SAC components on the outer kinetochores promotes chromosome instability (CIN) and tumorigenesis. Here, we study the expression of CENP-I, a key component of the HIKM complex at the inner kinetochores, in breast cancer, including ductal, lobular, medullary and male breast carcinomas...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751540/ttk-inhibitors-as-a-targeted-therapy-for-ctnnb1-%C3%AE-catenin-mutant-cancers
#14
Guido J R Zaman, Jeroen A D M de Roos, Marion A A Libouban, Martine B W Prinsen, Jos de Man, Rogier C Buijsman, Joost C M Uitdehaag
The spindle assembly checkpoint kinase TTK (Mps1) is a key regulator of chromosome segregation and is the subject of novel targeted therapy approaches by small molecule inhibitors. While the first TTK inhibitors have entered phase 1 dose escalating studies in combination with taxane chemotherapy, a patient stratification strategy is still missing. With the aim to identify a genomic biomarker to predict the response of tumor cells to TTK inhibitor therapy, we profiled a set of pre-clinical and clinical TTK inhibitors from different chemical series on a panel of sixty-six genetically characterized cell lines derived from different tumors (Oncolines)...
July 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28718377/downregulation-of-tyrosine-threonine-kinase-inhibits-tumor-growth-via-g2-m-arrest-in-human-endometrioid-endometrial-adenocarcinoma
#15
Jiamiao Zhang, Yan Jiang, Yu Zhao, Wanxue Wang, Yiran Xie, Huating Wang, Yihua Yang
Endometrial cancer is the most common gynecologic malignancy, about 80% of which is endometrial endometrioid carcinoma. Dysregulation of spindle assembly checkpoint plays a vital role in endometrial endometrioid carcinoma tumorigenesis and progression. The purpose of this study was to explore how tyrosine threonine kinase, a spindle assembly checkpoint-related protein, promotes the endometrial endometrioid carcinoma progression. We found that both messenger RNA and protein levels of tyrosine threonine kinase in endometrial endometrioid carcinoma tissues are higher than those in normal endometrial tissues, and its expression is associated with tumor stages...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28714568/exposure-to-reversine-affects-the-chondrocyte-morphology-and-phenotype-in-vitro
#16
S Gasparini, F Villa, L Molfetta, E Repaci, P Castagnola, R Quarto, P Giannoni
Articular chondrocytes derived from osteoarthritic tissues (OA-HAC) show a severely reduced chondrogenic commitment. This impairment undermines their use for tissue-engineered cartilage repair, which relies on cell proliferation and growth to meet the therapeutic needs but also on efficient cell plasticity to recover the chondrogenic phenotype. Reversine (Rev), a 2,6-disubstituted purine inhibitor of spindle-assembly checkpoints, was described to convert differentiated mesenchymal cells to their undifferentiated precursors...
July 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28711872/cell-scientist-to-watch-kevin-corbett
#17
(no author information available yet)
Kevin Corbett graduated in biology and biochemistry from the University of Virginia. He then went to the University of California, Berkeley, to work on the structure and function of DNA topoisomerases in bacteria and archaea for his PhD with James Berger. In 2005, he moved to the laboratory of Stephen Harrison at Harvard Medical School for his postdoctoral work on kinetochore structure and function, particularly the yeast monopolin complex, which promotes proper chromosome segregation in the first meiotic division...
July 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28695965/role-of-mad2-expression-during-the-early-development-of-the-sea-urchin
#18
Odile Bronchain, Wael Jdey, Laetitia Caraty, Brigitte Ciapa
Mitotic arrest deficient 2 (Mad2) belongs to the spindle assembly checkpoint (SAC), a mechanism that blocks progression of the cell cycle until microtubule attachment to kinetochores is complete. It has been found to be involved in the resistance of cancer cells to "anti-mitotic" drugs such as paclitaxel. Mad2 controls meiotic progression, but its role during sea urchin development had never been investigated. Furthermore, the existence of a SAC in this species had never been proved. The present data show that a Mad2 protein, highly homologous to that of humans, is expressed in this species...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28684541/consequences-of-mitotic-slippage-for-antimicrotubule-drug-therapy
#19
Bing Cheng, Karen Carmelina Crasta
Antimicrotubule agents are commonly utilized as front-line therapies against several malignancies, either by themselves or as combination therapies. Cell-based studies have pinpointed the anti-proliferative basis of action to be a consequence of perturbation of microtubule dynamics leading to sustained activation of the spindle assembly checkpoint, prolonged mitotic arrest and mitotic cell death. However, depending on the biological context and cell type, cells may take an alternative route besides mitotic cell death via a process known as mitotic slippage...
July 6, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28671988/checkpoints-of-apicomplexan-cell-division-identified-in-toxoplasma-gondii
#20
Carmelo A Alvarez, Elena S Suvorova
The unusual cell cycles of Apicomplexa parasites are remarkably flexible with the ability to complete cytokinesis and karyokinesis coordinately or postpone cytokinesis for several rounds of chromosome replication, and are well recognized. Despite this surprising biology, the molecular machinery required to achieve this flexibility is largely unknown. In this study, we provide comprehensive experimental evidence that apicomplexan parasites utilize multiple Cdk-related kinases (Crks) to coordinate cell division...
July 2017: PLoS Pathogens
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