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https://www.readbyqxmd.com/read/28211950/a-new-cell-cycle-checkpoint-that-senses-plasma-membrane-cell-wall-damage-in-budding-yeast
#1
Keiko Kono, Amy E Ikui
In nature, cells face a variety of stresses that cause physical damage to the plasma membrane and cell wall. It is well established that evolutionarily conserved cell cycle checkpoints monitor various cellular perturbations, including DNA damage and spindle misalignment. However, the ability of these cell cycle checkpoints to sense a damaged plasma membrane/cell wall is poorly understood. To the best of our knowledge, our recent paper described the first example of such a checkpoint, using budding yeast as a model...
February 17, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28202332/cdc20-at-the-crossroads-between-chromosome-segregation-and-mitotic-exit
#2
REVIEW
Maria Kapanidou, Natalie L Curtis, Victor M Bolanos-Garcia
Cell-division cycle protein 20 homologue (Cdc20) has important functions in chromosome segregation and mitotic exit. Cdc20 is the target of the spindle assembly checkpoint (SAC) and a key cofactor of the anaphase-promoting complex or cyclosome (APC/C) E3 ubiquitin ligase, thus regulating APC/C ubiquitin activity on specific substrates for their subsequent degradation by the proteasome. Here we discuss the roles of Cdc20 in SAC signalling and mitotic exit, describe how the integration of traditional approaches with emerging technologies has revealed new details of Cdc20 functions, comment about the potential of Cdc20 as a therapeutic target for the treatment of human malignancies, and discuss recent advances and controversies in the mechanistic understanding of the control of chromosome segregation during cell division...
February 12, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28188027/a-new-mode-of-mitotic-surveillance
#3
REVIEW
Bramwell G Lambrus, Andrew J Holland
Cells have evolved certain precautions to preserve their genomic content during mitosis and avoid potentially oncogenic errors. Besides the well-established DNA damage checkpoint and spindle assembly checkpoint (SAC), recent observations have identified an additional mitotic failsafe referred to as the mitotic surveillance pathway. This pathway triggers a cell cycle arrest to block the growth of potentially unfit daughter cells and is activated by both prolonged mitosis and centrosome loss. Recent genome-wide screens surprisingly revealed that 53BP1 and USP28 act upstream of p53 to mediate signaling through the mitotic surveillance pathway...
February 7, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28187452/pign-gene-expression-aberration-is-associated-with-genomic-instability-and-leukemic-progression-in-acute-myeloid-leukemia-with-myelodysplastic-features
#4
Emmanuel K Teye, Abigail Sido, Ping Xin, Niklas K Finnberg, Prashanth Gokare, Yuka I Kawasawa, Anna C Salzberg, Sara Shimko, Michael Bayerl, W Christopher Ehmann, David F Claxton, Witold B Rybka, Joseph J Drabick, Hong-Gang Wang, Thomas Abraham, Wafik S El-Deiry, Robert A Brodsky, Raymond J Hohl, Jeffrey J Pu
Previous studies have linked increased frequency of glycosylphosphatidylinositol-anchor protein (GPI-AP) deficiency with genomic instability and the risk of carcinogenesis. However, the underlying mechanism is still not clear. A randomForest analysis of the gene expression array data from 55 MDS patients (GSE4619) demonstrated a significant (p = 0.0007) correlation (Pearson r =-0.4068) between GPI-anchor biosynthesis gene expression and genomic instability, in which PIGN, a gene participating in GPI-AP biosynthesis, was ranked as the third most important in predicting risk of MDS progression...
7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178520/identification-of-a-sgo2-dependent-but-mad2-independent-pathway-controlling-anaphase-onset-in-fission-yeast
#5
John C Meadows, Theresa C Lancaster, Graham J Buttrick, Alicja M Sochaj, Liam J Messin, Maria Del Mar Mora-Santos, Kevin G Hardwick, Jonathan B A Millar
The onset of anaphase is triggered by activation of the anaphase-promoting complex/cyclosome (APC/C) following silencing of the spindle assembly checkpoint (SAC). APC/C triggers ubiquitination of Securin and Cyclin B, which leads to loss of sister chromatid cohesion and inactivation of Cyclin B/Cdk1, respectively. This promotes relocalization of Aurora B kinase and other components of the chromosome passenger complex (CPC) from centromeres to the spindle midzone. In fission yeast, this is mediated by Clp1 phosphatase-dependent interaction of CPC with Klp9/MKLP2 (kinesin-6)...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28174095/anti-mitotic-agents-are-they-emerging-molecules-for-cancer-treatment
#6
REVIEW
Larissa Siqueira Penna, João Antonio Pêgas Henriques, Diego Bonatto
Mutations in cancer cells frequently result in cell cycle alterations that lead to unrestricted growth compared to normal cells. Considering this phenomenon, many drugs have been developed to inhibit different cell-cycle phases. Mitotic phase targeting disturbs mitosis in tumor cells, triggers the spindle assembly checkpoint and frequently results in cell death. The first anti-mitotics to enter clinical trials aimed to target tubulin. Although these drugs improved the treatment of certain cancers, and many anti-microtubule compounds are already approved for clinical use, severe adverse events such as neuropathies were observed...
February 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28159965/mitotic-spindle-disruption-in-human-preimplantation-embryos-activates-the-spindle-assembly-checkpoint-but-not-apoptosis-until-day-5-of-development
#7
K Jacobs, H Van de Velde, C De Paepe, K Sermon, C Spits
No abstract text is available yet for this article.
February 4, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28157697/trip13-impairs-mitotic-checkpoint-surveillance-and-is-associated-with-poor-prognosis-in-multiple-myeloma
#8
Yi Tao, Guang Yang, Hongxing Yang, Dongliang Song, Liangning Hu, Bingqian Xie, Houcai Wang, Lu Gao, Minjie Gao, Hongwei Xu, Zhijian Xu, Xiaosong Wu, Yiwen Zhang, Weiliang Zhu, Fenghuang Zhan, Jumei Shi
AAA-ATPase TRIP13 is one of the chromosome instability gene recently established in multiple myeloma (MM), the second most common and incurable hematological malignancy. However, the specific function of TRIP13 in MM is largely unknown. Using sequential gene expression profiling, we demonstrated that high TRIP13 expression levels were positively correlated with progression, disease relapse, and poor prognosis in MM patients. Overexpressing human TRIP13 in myeloma cells prompted cell growth and drug resistance, and overexpressing murine TRIP13, which shares 93% sequence identity with human TRIP13, led to colony formation of NIH/3T3 fibroblasts in vitro and tumor formation in vivo...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28118058/smc1%C3%AE-is-required-for-activation-of-sac-during-mouse-oocyte-meiosis
#9
Yilong Miao, Changyin Zhou, Zhaokang Cui, Xiaoxin Dai, Mianqun Zhang, Yajuan Lu, Bo Xiong
Smc1β is a meiosis-specific cohesin subunit that is essential for sister chromatid cohesion and DNA recombination. Previous studies have shown that Smc1β-deficient mice in both sexes are sterile. Ablation of Smc1β during male meiosis leads to the blockage of spermatogenesis in pachytene stage, and ablation of Smc1β during female meiosis generates a highly error-prone oocyte although it could develop to metaphase II stage. However, the underlying mechanisms regarding how Smc1β maintains the correct meiotic progression in mouse oocytes have not been clearly defined...
January 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28117323/temporal-and-compartment-specific-signals-coordinate-mitotic-exit-with-spindle-position
#10
Ayse Koca Caydasi, Anton Khmelinskii, Rafael Duenas-Sanchez, Bahtiyar Kurtulmus, Michael Knop, Gislene Pereira
The spatiotemporal control of mitotic exit is crucial for faithful chromosome segregation during mitosis. In budding yeast, the mitotic exit network (MEN) drives cells out of mitosis, whereas the spindle position checkpoint (SPOC) blocks MEN activity when the anaphase spindle is mispositioned. How the SPOC operates at a molecular level remains unclear. Here, we report novel insights into how mitotic signalling pathways orchestrate chromosome segregation in time and space. We establish that the key function of the central SPOC kinase, Kin4, is to counterbalance MEN activation by the cdc fourteen early anaphase release (FEAR) network in the mother cell compartment...
January 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28105232/trip13-is-expressed-in-colorectal-cancer-and-promotes-cancer-cell-invasion
#11
Kenji Kurita, Masao Maeda, Mohammed A Mansour, Toshio Kokuryo, Keisuke Uehara, Yukihiro Yokoyama, Masato Nagino, Michinari Hamaguchi, Takeshi Senga
Thyroid hormone receptor interactor 13 (TRIP13) is a member of the ATPases associated with various cellular activities family of proteins and is highly conserved in a wide range of species. Recent studies have demonstrated that TRIP13 is critical for the inactivation of the spindle assembly checkpoint and is associated with the progression of certain cancers. In the present study, the role of TRIP13 in colorectal cancer (CRC) was examined. Reverse transcription-quantitative polymerase chain reaction analysis revealed that TRIP13 messenger RNA was highly expressed in multiple CRC tissues...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28102834/basis-of-catalytic-assembly-of-the-mitotic-checkpoint-complex
#12
Alex C Faesen, Maria Thanasoula, Stefano Maffini, Claudia Breit, Franziska Müller, Suzan van Gerwen, Tanja Bange, Andrea Musacchio
Accurate genome inheritance by daughter cells requires that sister chromatids in the mother attach to microtubules emanating from opposite poles of the mitotic spindle (bi-orientation). A surveillance mechanism named the spindle assembly checkpoint (SAC) monitors the microtubule attachment process, temporarily halting sister chromatid separation and mitotic exit until completion of bi-orientation1. SAC failure results in abnormal chromosome numbers (aneuploidy), a hallmark of many tumours. The HORMA domain protein MAD2 is a subunit of the SAC effector mitotic checkpoint complex (MCC)...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/28101375/aurora-a-promotes-the-establishment-of-spindle-assembly-checkpoint-by-priming-the-haspin-aurora-b-feedback-loop-in-late-g2-phase
#13
Fazhi Yu, Ya Jiang, Lucy Lu, Mimi Cao, Yulong Qiao, Xing Liu, Dan Liu, Terry Van Dyke, Fangwei Wang, Xuebiao Yao, Jing Guo, Zhenye Yang
Aurora-A kinase functions mainly in centrosome maturation, separation and spindle formation. It has also been found to be amplified or overexpressed in a range of solid tumors, which is linked with tumor progression and poor prognosis. Importantly, Aurora-A inhibitors are being studied in a number of ongoing clinical trials. However, whether and how Aurora-A has a role in the regulation of the mitotic checkpoint is controversial. Additionally, the function of nuclear-accumulated Aurora-A in late G2 phase is not clear...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28079247/dynamic-location-changes-of-bub1-phosphorylated-h2athr133-with-cenh3-nucleosome-in-maize-centromeric-regions
#14
Handong Su, Yalin Liu, Qianhua Dong, Chao Feng, Jing Zhang, Yang Liu, James A Birchler, Fangpu Han
The genomic stability of all organisms requires precise cell division with proper chromosome orientation. The Bub1-H2Aph-Sgo1 pathway and spindle assembly checkpoint (SAC) components have been identified in yeast and mammals that are important for sister centromere orientation and chromosome segregation. However, their roles in plants are not clear. Maize meiotic mutants and minichromosomes were used to study the role of H2AThr133 phosphorylation and SAC components in sister centromere orientation and chromosome segregation...
January 12, 2017: New Phytologist
https://www.readbyqxmd.com/read/28073664/extract-of-bulbus-fritillaria-cirrhosa-perturbs-spindle-assembly-checkpoint-induces-mitotic-aberrations-and-genomic-instability-in-human-colon-epithelial-cell-line
#15
Xihan Guo, Juan Ni, Jinglun Xue, Xu Wang
BACKGROUND: Bulbus Fritillaria cirrhosa D. Don (BFC) has been used in China as a folk medicine for the treatment of cough and asthma for more than 2000 years. The antitussive and antiasthmatic effects of BFC have been reported before, nevertheless its toxicity and safety have not been documented. This study investigated the possible effects of BFC on spindle assembly checkpoint (SAC), mitotic fidelity and genomic stability in human NCM460 colon epithelial cells. METHODS: Cells were treated with BFC (0, 20, 40, 80 and 160μg/ml) for 24, 48 and 72h and harvested differently according to the biomarkers observed...
January 7, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28072388/a-sequential-multi-target-mps1-phosphorylation-cascade-promotes-spindle-checkpoint-signaling
#16
Zhejian Ji, Haishan Gao, Luying Jia, Bing Li, Hongtao Yu
The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C(Cdc20)) to delay anaphase onset...
January 10, 2017: ELife
https://www.readbyqxmd.com/read/28069571/apc-c-dysfunction-limits-excessive-cancer-chromosomal-instability
#17
Laurent Sansregret, James O Patterson, Sally Dewhurst, Carlos López-García, André Koch, Nicholas McGranahan, William Chong Hang Chao, David J Barry, Andrew Rowan, Rachael Instrell, Stuart Horswell, Michael Way, Michael Howell, Martin R Singleton, René H Medema, Paul Nurse, Mark Petronczki, Charles Swanton
: Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization...
February 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28069132/molecular-regulation-of-the-spindle-assembly-checkpoint-by-kinases-and-phosphatases
#18
G Manic, F Corradi, A Sistigu, S Siteni, I Vitale
The spindle assembly checkpoint (SAC) is a surveillance mechanism contributing to the preservation of genomic stability by monitoring the microtubule attachment to, and/or the tension status of, each kinetochore during mitosis. The SAC halts metaphase to anaphase transition in the presence of unattached and/or untensed kinetochore(s) by releasing the mitotic checkpoint complex (MCC) from these improperly-oriented kinetochores to inhibit the anaphase-promoting complex/cyclosome (APC/C). The reversible phosphorylation of a variety of substrates at the kinetochore by antagonistic kinases and phosphatases is one major signaling mechanism for promptly turning on or turning off the SAC...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28049706/coordination-of-cell-cycle-progression-and-mitotic-spindle-assembly-involves-histone-h3-lysine-4-methylation-by-set1-compass
#19
Traude H Beilharz, Paul F Harrison, Douglas Maya Miles, Michael Ming See, Uyen Minh Merry Le, Ming Kalanon, Melissa Jane Curtis, Qambar Hasan, Julie Saksouk, Thanasis Margaritis, Frank Holstege, Vincent Geli, Bernhard Dichtl
Methylation of histone H3 lysine 4 (H3K4) by Set1 complex/COMPASS is a hallmark of eukaryotic chromatin, but it remains poorly understood how this post-translational modification contributes to the regulation of biological processes like the cell cycle. Here, we report a H3K4 methylation-dependent pathway in Saccharomyces cerevisiae that governs toxicity toward benomyl, a microtubule destabilizing drug. Benomyl-sensitive growth of wild-type cells required mono- and dimethylation of H3K4 and Pho23, a PHD-containing subunit of the Rpd3L complex...
January 2017: Genetics
https://www.readbyqxmd.com/read/28040741/premature-silencing-of-the-spindle-assembly-checkpoint-is-prevented-by-the-bub1-h2a-sgo1-pp2a-axis-in-saccharomyces-cerevisiae
#20
Fengzhi Jin, Michael Bokros, Yanchang Wang
The spindle assembly checkpoint (SAC) monitors mistakes in kinetochore-microtubule interaction and its activation prevents anaphase entry. The SAC remains active until all chromosomes have achieved bipolar attachment that applies tension on kinetochores. Our previous data in budding yeast Saccharomyces cerevisiae show that Ipl1/Aurora B kinase and a centromere-associated protein Sgo1 are required to prevent SAC silencing prior to tension generation, but we believe that this regulatory network is incomplete...
December 30, 2016: Genetics
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