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Spindle Assembly Checkpoint

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https://www.readbyqxmd.com/read/29342242/meiotic-spindle-formation-in-mammalian-oocytes-implications-for-human-infertility
#1
Suk Namgoong, Nam-Hyung Kim
In the final stage of oogenesis, mammalian oocytes generate a meiotic spindle and undergo chromosome segregation to yield an egg that is ready for fertilization. Herein, we describe the recent advances in understanding the mechanisms controlling formation of the meiotic spindle in metaphase I (MI) and metaphase II (MII) in mammalian oocytes, and focus on the differences between mouse and human oocytes. Unlike mitotic cells, mammalian oocytes lack typical centrosomes that consist of two centrioles and the surrounding pericentriolar matrix proteins (PCM), which serve as microtubule-organizing centers (MTOCs) in most somatic cells...
January 12, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29321280/analysis-of-mitotic-checkpoint-function-in-xenopus-egg-extracts
#2
Yinghui Mao
Accurate sister chromatid segregation is pivotal in the faithful transmission of genetic information during each cell division. To ensure accurate segregation, eukaryotic organisms have evolved a "mitotic (or spindle assembly) checkpoint" to prevent premature advance to anaphase before successful attachment of every chromosome to the microtubules of the mitotic spindle. An unattached kinetochore generates a diffusible signal that inhibits ubiquitination of substrates such as cyclin B and securins. This protocol presents an in vitro assay for studying the mitotic checkpoint using Xenopus laevis egg extracts...
January 10, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29307372/biphasic-regulation-of-spindle-assembly-checkpoint-by-low-and-high-concentrations-of-resveratrol-leads-to-the-opposite-effect-on-chromosomal-instability
#3
Xihan Guo, Juan Ni, Xueqin Dai, Tao Zhou, Guofang Yang, Jinglun Xue, Xu Wang
Resveratrol (RSV) is a naturally occurring polyphenolic phytoalexin possessing numerous health-promoting effects. Chromosomal instability (CIN), usually results from defective spindle assembly checkpoint (SAC), is a major contributor to many diseases. While it's recently recognized that RSV exhibits a nonlinear dose response for disease prevention, whether it's the case for its role in CIN remains unknown. Here, we investigated the potential of a broad range of RSV concentrations (0.01-100μM) on CIN and the underlying mechanisms in human normal colon epithelial NCM460 cells...
January 2018: Mutation Research
https://www.readbyqxmd.com/read/29283376/differential-selective-pressures-experienced-by-the-aurora-kinase-gene-family
#4
Joni M Seeling, Alexis A Farmer, Adam Mansfield, Hyuk Cho, Madhusudan Choudhary
Aurora kinases (AKs) are serine/threonine kinases that are essential for cell division. Humans have three AK genes: AKA, AKB, and AKC. AKA is required for centrosome assembly, centrosome separation, and bipolar spindle assembly, and its mutation leads to abnormal spindle morphology. AKB is required for the spindle checkpoint and proper cytokinesis, and mutations cause chromosome misalignment and cytokinesis failure. AKC is expressed in germ cells, and has a role in meiosis analogous to that of AKB in mitosis...
December 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29276128/tension-induced-error-correction-and-not-kinetochore-attachment-status-activates-the-sac-in-an-aurora-b-c-dependent-manner-in-oocytes
#5
Antoine Vallot, Ioanna Leontiou, Damien Cladière, Warif El Yakoubi, Susanne Bolte, Eulalie Buffin, Katja Wassmann
Cell division with partitioning of the genetic material should take place only when paired chromosomes named bivalents (meiosis I) or sister chromatids (mitosis and meiosis II) are correctly attached to the bipolar spindle in a tension-generating manner. For this to happen, the spindle assembly checkpoint (SAC) checks whether unattached kinetochores are present, in which case anaphase onset is delayed to permit further establishment of attachments. Additionally, microtubules are stabilized when they are attached and under tension...
December 16, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29244163/regulation-of-chromosome-segregation-in-oocytes-and-the-cellular-basis-for-female-meiotic-errors
#6
Jessica Greaney, Zhe Wei, Hayden Homer
BACKGROUND: Meiotic chromosome segregation in human oocytes is notoriously error-prone, especially with ageing. Such errors markedly reduce the reproductive chances of increasing numbers of women embarking on pregnancy later in life. However, understanding the basis for these errors is hampered by limited access to human oocytes. OBJECTIVE AND RATIONALE: Important new discoveries have arisen from molecular analyses of human female recombination and aneuploidy along with high-resolution analyses of human oocyte maturation and mouse models...
December 13, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/29228672/pten-regulates-spindle-assembly-checkpoint-timing-through-mad1-in-interphase
#7
Yu Liu, Xiao Du, Shuting Zhang, Yang Liu, Qiaoling Zhang, Qi Yin, Michael A McNutt, Yuxin Yin
The spindle assembly checkpoint (SAC) restrains anaphase progression to ensure all chromosomes attach properly to the spindle. Although SAC timing has been extensively investigated in mitosis, its mechanism of regulation in interphase is unclear. We report that PTEN functions as a crucial activator of SAC timing and protects chromosome segregation under both spindle poison treated and untreated conditions. We show that PTEN physically interacts with MAD1 and promotes its dimerization and localization in the nuclear pore...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209640/some-assembly-required-redefining-the-mitotic-checkpoint
#8
John C Meadows, Jonathan B A Millar
The spindle assembly checkpoint (also known as the spindle or mitotic checkpoint) is a surveillance system that ensures fidelity of chromosome segregation. Here we suggest, in light of historical and more recent evidence, that this signaling system monitors kinetochore attachment and spindle assembly by two distinct, but functionally overlapping, pathways.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29196757/mitotic-slippage-and-the-subsequent-cell-fates-after-inhibition-of-aurora-b-during-tubulin-binding-agent-induced-mitotic-arrest
#9
Yasuo Tsuda, Makoto Iimori, Yuichiro Nakashima, Ryota Nakanishi, Koji Ando, Kippei Ohgaki, Hiroyuki Kitao, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara
Tubulin-binding agents (TBAs) are designed to target microtubule (MT) dynamics, resulting in compromised mitotic spindles and an unsatisfied spindle assembly checkpoint. The activity of Aurora B kinase is indispensable for TBA-induced mitotic arrest, and its inhibition causes mitotic slippage and postmitotic endoreduplication. However, the precise phenomenon underlying mitotic slippage, which is caused by treatment with both Aurora B inhibitors and TBAs, and the cell fate after postmitotic slippage are not completely understood...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29196303/whole-chromosome-loss-and-associated-breakage-fusion-bridge-cycles-transform-mouse-tetraploid-cells
#10
Rozario Thomas, Daniel Henry Marks, Yvette Chin, Robert Benezra
Whole chromosome gains or losses (aneuploidy) are a hallmark of ~70% of human tumors. Modeling the consequences of aneuploidy has relied on perturbing spindle assembly checkpoint (SAC) components, but interpretations of these experiments are clouded by the multiple functions of these proteins. Here, we used a Cre recombinase-mediated chromosome loss strategy to individually delete mouse chromosomes 9, 10, 12, or 14 in tetraploid immortalized murine embryonic fibroblasts. This methodology also involves the generation of a dicentric chromosome intermediate, which subsequently undergoes a series of breakage-fusion-bridge (BFB) cycles...
December 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29192061/nude-l-regulates-dynein-at-kinetochores-but-is-dispensable-for-other-dynein-functions-in-the-c-elegans-early-embryo
#11
Patrícia A Simões, Ricardo Celestino, Ana X Carvalho, Reto Gassmann
In mitosis, the molecular motor dynein is recruited to kinetochores by the Rod-Zw10-Zwilch complex (RZZ) and Spindly to control spindle assembly checkpoint (SAC) signaling and microtubule attachment. How the ubiquitous dynein co-factors Lis1 and NudE/L contribute to these functions remains poorly understood. Here, we show that the C. elegans NudE/L homolog NUD-2 is dispensable for dynein- and LIS-1-dependent mitotic spindle assembly in the zygote. This facilitates functional characterization of kinetochore-localized NUD-2, which is recruited by the CENP-F-like proteins HCP-1/2 independently of RZZ-Spindly and dynein-LIS-1...
November 30, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29190829/a-comprehensive-analysis-of-breast-cancer-microbiota-and-host-gene-expression
#12
Kevin J Thompson, James N Ingle, Xiaojia Tang, Nicholas Chia, Patricio R Jeraldo, Marina R Walther-Antonio, Karunya K Kandimalla, Stephen Johnson, Janet Z Yao, Sean C Harrington, Vera J Suman, Liewei Wang, Richard L Weinshilboum, Judy C Boughey, Jean-Pierre Kocher, Heidi Nelson, Matthew P Goetz, Krishna R Kalari
The inflammatory tumoral-immune response alters the physiology of the tumor microenvironment, which may attenuate genomic instability. In addition to inducing inflammatory immune responses, several pathogenic bacteria produce genotoxins. However the extent of microbial contribution to the tumor microenvironment biology remains unknown. We utilized The Cancer Genome Atlas, (TCGA) breast cancer data to perform a novel experiment utilizing unmapped and mapped RNA sequencing read evidence to minimize laboratory costs and effort...
2017: PloS One
https://www.readbyqxmd.com/read/29186573/conformational-dynamics-of-the-hop1-horma-domain-reveal-a-common-mechanism-with-the-spindle-checkpoint-protein-mad2
#13
Alan M V West, Elizabeth A Komives, Kevin D Corbett
The HORMA domain is a highly conserved protein-protein interaction module found in eukaryotic signaling proteins including the spindle assembly checkpoint protein Mad2 and the meiotic HORMAD proteins. HORMA domain proteins interact with short 'closure motifs' in partner proteins by wrapping their C-terminal 'safety belt' region entirely around these motifs, forming topologically-closed complexes. Closure motif binding and release requires large-scale conformational changes in the HORMA domain, but such changes have only been observed in Mad2...
November 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29180432/phosphorylation-of-cenp-c-by-aurora-b-facilitates-kinetochore-attachment-error-correction-in-mitosis
#14
Xing Zhou, Fan Zheng, Chengliang Wang, Minhao Wu, Xiaozhen Zhang, Qian Wang, Xuebiao Yao, Chuanhai Fu, Xuan Zhang, Jianye Zang
Kinetochores are superprotein complexes that orchestrate chromosome segregation via a dynamic interaction with spindle microtubules. A physical connection between CENP-C and the Mis12-Ndc80-Knl1 (KMN) protein network is an important pathway that is used to assemble kinetochores on CENP-A nucleosomes. Multiple outer kinetochore components are phosphorylated by Aurora B kinase to activate the spindle assembly checkpoint (SAC) and to ensure accurate chromosome segregation. However, it is unknown whether Aurora B can phosphorylate inner kinetochore components to facilitate proper mitotic chromosome segregation...
November 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29167309/visualizing-the-complex-functions-and-mechanisms-of-the-anaphase-promoting-complex-cyclosome-apc-c
#15
REVIEW
Claudio Alfieri, Suyang Zhang, David Barford
The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two decades since its discovery, much has been learnt concerning its role in recognizing and ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms governing substrate specificity, the catalytic process of assembling polyubiquitin chains on its target proteins, and its regulation by phosphorylation and the spindle assembly checkpoint...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29165592/folate-deficiency-induces-mitotic-aberrations-and-chromosomal-instability-by-compromising-the-spindle-assembly-checkpoint-in-cultured-human-colon-cells
#16
Xihan Guo, Juan Ni, Yuqian Zhu, Tao Zhou, Xiaoling Ma, Jinglun Xue, Xu Wang
Folates comprise the essential B9 vitamin that act as cofactors and cosubstrates in one-carbon metabolism for both biosynthesis and methylation of DNA and RNA. Folate deficiency (FD) has been shown to induce chromosomal instability (CIN), yet the underlying mechanisms are poorly understood. Here, we used human NCM460 colon mucosal cells as a model to investigate the effect of FD on spindle assembly checkpoint (SAC), a cell-cycle regulatory pathway preventing CIN during mitosis. Cells were maintained in medium containing 1...
November 19, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29161843/mathematical-analysis-and-modeling-of-dna-segregation-mechanisms
#17
Bashar Ibrahim
The precise regulation of cell life division is indispensable to the reliable inheritance of genetic material, i.e. DNA, in successive generations of cells. This is governed by dedicated biochemical networks which ensure that all requirements are met before transition from one phase to the next. The Spindle Assembly Checkpoint (SAC) is an evolutionarily mechanism that delays mitotic progression until all chromosomes are properly linked to the mitotic spindle. During some asymmetric cell divisions, such as those observed in budding yeast, an additional mechanism, the Spindle Position Checkpoint (SPOC), is required to delay exit from mitosis until the mitotic spindle is correctly aligned...
April 1, 2018: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/29158164/lmo7-exerts-an-effect-on-mitosis-progression-and-the-spindle-assembly-checkpoint
#18
Yao-Wei Tzeng, Dai-Yu Li, Yvan Chen, Cheng-Hsiu Yang, Chih-Yun Chang, Yue-Li Juang
LMO7 (LIM domain only 7) is a transcription regulator for expression of many Emery-Dreifuss muscular dystrophy-relevant genes, and binds to α-actinin and AF6/afadin at adherens junctions for epithelial cell-cell adhesion. In this study, we found that human LMO7 interacted with the spindle assembly checkpoint (SAC) protein MAD1. LMO7 colocalized with actin filaments at the cell membrane but did not colocalize with MAD1 at kinetochores in prometaphase. Our observations reveal that overexpression but not depletion of LMO7 caused a SAC defect, and that the LIM domain of LMO7 was a determinant of its ability to interfere with kinetochore localization of the SAC proteins MAD2 and BUBR1 and cause a SAC defect though the LIM peptide itself did neither bind to MAD1, MAD2 and BUBR1 nor localize to the actin filaments...
November 17, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29147457/oxidative-stress-delays-prometaphase-metaphase-of-the-first-cleavage-in-mouse-zygotes-via-the-mad2l1-mediated-spindle-assembly-checkpoint
#19
Que Wu, Zhiling Li, Yue Huang, Diting Qian, Man Chen, Wanfen Xiao, Bin Wang
In zygotes, DNA damage delays the first cleavage to enable repair. Our previous study found that 0.03 mM hydrogen peroxide (H2O2) was the minimum concentration required for induction of oxidative DNA damage in mouse zygotes and that this represented the most similar situation to the clinical phenomenon. In this study, we quantified the cleavage rates of cells in blastocysts at different developmental stages, followed by immunofluorescence to detect activation of γ-H2A histone family member X (a marker of DNA damage) in zygotes to confirm that oxidative DNA damage was induced in H2O2-treated zygotes...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29129638/an-attachment-independent-biochemical-timer-of-the-spindle-assembly-checkpoint
#20
Junbin Qian, Maria Adelaida García-Gimeno, Monique Beullens, Maria Giulia Manzione, Gerd Van der Hoeven, Juan Carlos Igual, Miguel Heredia, Pascual Sanz, Lendert Gelens, Mathieu Bollen
The spindle assembly checkpoint (SAC) generates a diffusible protein complex that prevents anaphase until all chromosomes are properly attached to spindle microtubules. A key step in SAC initiation is the recruitment of MAD1 to kinetochores, which is generally thought to be governed by the microtubule-kinetochore (MT-KT) attachment status. However, we demonstrate that the recruitment of MAD1 via BUB1, a conserved kinetochore receptor, is not affected by MT-KT interactions in human cells. Instead, BUB1:MAD1 interaction depends on BUB1 phosphorylation, which is controlled by a biochemical timer that integrates counteracting kinase and phosphatase effects on BUB1 into a pulse-generating incoherent feedforward loop...
November 16, 2017: Molecular Cell
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