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Geetha S Hewawasam, Karthik Dhatchinamoorthy, Mark Mattingly, Chris Seidel, Jennifer L Gerton
Correct localization of the centromeric histone variant CenH3/CENP-A/Cse4 is an important part of faithful chromosome segregation. Mislocalization of CenH3 could affect chromosome segregation, DNA replication and transcription. CENP-A is often overexpressed and mislocalized in cancer genomes, but the underlying mechanisms are not understood. One major regulator of Cse4 deposition is Psh1, an E3 ubiquitin ligase that controls levels of Cse4 to prevent deposition into non-centromeric regions. We present evidence that Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved histone H3/H4 chaperone with subunits shown previously to interact with CenH3 in flies and human cells, regulates Cse4 deposition in budding yeast...
March 7, 2018: Nucleic Acids Research
Christian Hoischen, Sibel Yavas, Thorsten Wohland, Stephan Diekmann
Kinetochore proteins assemble onto centromeric chromatin and regulate DNA segregation during cell division. The inner kinetochore proteins bind centromeres while most outer kinetochore proteins assemble at centromeres during mitosis, connecting the complex to microtubules. Here, we measured the co-migration between protein pairs of the constitutive centromere associated network (CCAN) and hMis12 complexes by fluorescence cross-correlation spectroscopy (FCCS) in the nucleoplasm outside centromeres in living human interphase cells...
2018: PloS One
Abhishek Sadhu, Ilika Ghosh, Yuji Moriyasu, Anita Mukherjee, Maumita Bandyopadhyay
The effect of cerium oxide nanoparticle (CeNP) in plants has elicited substantial controversy. While some investigators have reported that CeNP possesses antioxidant properties, others observed CeNP to induce reactive oxygen species (ROS). In spite of considerable research carried out on the effects of CeNP in metazoans, fundamental studies that can unveil its intracellular consequences linking ROS production, autophagy and DNA damage are lacking in plants. To elucidate the impact of CeNP within plant cells, tobacco BY-2 cells were treated with 10, 50 and 250 µg ml-1 CeNP (Ce10, Ce50 and Ce250), for 24 h...
February 28, 2018: Mutagenesis
Go Itoh, Masanori Ikeda, Kenji Iemura, Mohammed Abdhullahel Amin, Sei Kuriyama, Masamitsu Tanaka, Natsuki Mizuno, Hiroko Osakada, Tokuko Haraguchi, Kozo Tanaka
Faithful chromosome segregation is ensured by the establishment of bi-orientation; the attachment of sister kinetochores to the end of microtubules extending from opposite spindle poles. In addition, kinetochores can also attach to lateral surfaces of microtubules; called lateral attachment, which plays a role in chromosome capture and transport. However, molecular basis and biological significance of lateral attachment are not fully understood. We have addressed these questions by focusing on the prometaphase rosette, a typical chromosome configuration in early prometaphase...
March 1, 2018: Scientific Reports
Yuriko Nakano, Asumi Ochiai, Keisuke Kawamoto, Ayaka Takeda, Kenta Ichiyoshi, Toshihiko Ohnuki, Michael F Hochella, Satoshi Utsunomiya
To understand the competing effects of the components in extracellular substances (ES), polymeric substances (PS) and low-molecular-weight small substances (SS) <1 kDa derived from microorganisms, on the colloidal stability of cerium dioxide nanoparticles (CeNPs), we investigated their adsorption to sparingly soluble CeNPs at room temperature at pH 6.0. The ES was extracted from the fungus S. cerevisiae. The polypeptides and phosphates in all components preferentially adsorbed onto the CeNPs. The zeta potentials of ES + CeNPs, PS + CeNPs, and SS + CeNPs overlapped on the plot of PS itself, indicating the surface charge of the polymeric substances controls the zeta potentials...
February 26, 2018: Scientific Reports
Jonathan Nye, Daniël P Melters, Yamini Dalal
Histone chaperones are indispensable regulators of chromatin structure and function. Recent work has shown that they are frequently mis-regulated in cancer, which can have profound consequences on tumor growth and survival. Here, we focus on chaperones for the essential H3 histone variants H3.3 and CENP-A, specifically HIRA, DAXX/ATRX, DEK, and HJURP. This review summarizes recent studies elucidating their roles in regulating chromatin and discusses how cancer-specific chromatin interactions can be exploited to target cancer cells...
2018: F1000Research
Mohammed A Amin, Richard J McKenney, Dileep Varma
Chromosome alignment and segregation during mitosis require kinetochore-microtubule (kMT) attachments that are mediated by the molecular motor dynein and the kMT-binding complex Ndc80. The Rod-ZW10-Zwilch (RZZ) complex is central to this coordination, as it has an important role in dynein recruitment and has recently been reported to have a key function in the regulation of stable kMT attachments in Caenorhabditis elegans, besides its role in activating the spindle assembly checkpoint (SAC). However, the mechanism by which these protein complexes control kMT attachments to drive chromosome motility during early mitosis is still unclear...
February 23, 2018: Journal of Biological Chemistry
Chunguang Li, Liangtao Luo, Sheng Wei, Xiongbiao Wang
Invasive ductal carcinoma (IDC) is a common histological type of breast cancer. The aim of this study was to identify the potential crucial genes associated with IDC and to provide valid biological information for further investigations. The gene expression profiles of GSE10780 which contained 42 histologically normal breast tissues and 143 IDC tissues were downloaded from the GEO database. Functional and pathway enrichment analysis of differentially expressed genes (DEGs) were performed and protein-protein interaction (PPI) network was analyzed using Cytoscape...
January 23, 2018: Oncotarget
Jan G Ruppert, Kumiko Samejima, Melpomeni Platani, Oscar Molina, Hiroshi Kimura, A Arockia Jeyaprakash, Shinya Ohta, William C Earnshaw
The chromosomal passenger complex (CPC) is directed to centromeres during mitosis via binding to H3T3ph and Sgo1. Whether and how heterochromatin protein 1α (HP1α) influences CPC localisation and function during mitotic entry is less clear. Here, we alter HP1α dynamics by fusing it to a CENP-B DNA-binding domain. Tethered HP1 strongly recruits the CPC, destabilising kinetochore-microtubule interactions and activating the spindle assembly checkpoint. During mitotic exit, the tethered HP1 traps active CPC at centromeres...
February 21, 2018: EMBO Journal
Ana García Del Arco, Bruce A Edgar, Sylvia Erhardt
Stem cells of the Drosophila midgut (ISCs) are the only mitotically dividing cells of the epithelium and, therefore, presumably the only epithelial cells that require functional kinetochores for microtubule spindle attachment during mitosis. The histone variant CENP-A marks centromeric chromatin as the site of kinetochore formation and spindle attachment during mitotic chromosome segregation. Here, we show that centromeric proteins distribute asymmetrically during ISC division. Whereas newly synthesized CENP-A is enriched in differentiating progeny, CENP-C is undetectable in these cells...
February 20, 2018: Cell Reports
Michael Shaofei Zhang, Maiko Furuta, Alexei Arnaoutov, Mary Dasso
RCC1 associates to chromatin dynamically within mitosis and catalyzes Ran-GTP production. Exogenous RCC1 disrupts kinetochore structure in Xenopus egg extracts (XEEs), but the molecular basis of this disruption remains unknown. We have investigated this question, utilizing replicated chromosomes that possess paired sister kinetochores. We find that exogenous RCC1 evicts a specific subset of inner KT proteins including Shugoshin-1 (Sgo1) and the chromosome passenger complex (CPC). We generated RCC1 mutants that separate its enzymatic activity and chromatin binding...
February 21, 2018: Cell Cycle
Irfan Ahmad Bhat, Mir Ishfaq Nazir, Irshad Ahmad, Gireesh-Babu Pathakota, T I Chanu, Mukunda Goswami, J K Sundaray, Rupam Sharma
Chitosan nanoparticles (CNPs) have been proven considerable delivery agents due to their remarkable physicochemical properties. Present study reports the fabrication of CNPs by ionic gelation process and their characterization by different approaches. The constructed nanoparticles were successfully conjugated with eurycomanone with significant entrapment efficiency. Particle size of chitosan and chitosan conjugated eurycomanone nanoparticles were 126.2 nm and 130 nm respectively. Scanning electron microscopy showed that the particles were spherical in shape and well dispersed...
February 12, 2018: International Journal of Biological Macromolecules
Sonali Bhattacharjee, Fekret Osman, Laura Feeney, Alexander Lorenz, Claire Bryer, Matthew C Whitby
No abstract text is available yet for this article.
February 2018: Open Biology
Kentaro Ohkuni, Reuben Levy-Myers, Jack Warren, Wei-Chun Au, Yoshimitsu Takahashi, Richard E Baker, Munira A Basrai
Stringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4...
February 5, 2018: G3: Genes—Genomes—Genetics
Minkyoung Lee, Ik Soo Kim, Koog Chan Park, Jong-Seo Kim, Sung Hee Baek, Keun Il Kim
Mis18α, a component of Mis18 complex comprising of Mis18α, Mis18β, and M18BP1, is known to localize at the centromere from late telophase to early G1 phase and plays a priming role in CENP-A deposition. Although its role in CENP-A deposition is well established, the other function of Mis18α remains unknown. Here, we elucidate a new function of Mis18α that is critical for the proper progression of cell cycle independent of its role in CENP-A deposition. We find that Aurora B kinase phosphorylates Mis18α during mitosis not affecting neither centromere localization of Mis18 complex nor centromere loading of CENP-A...
January 5, 2018: Oncotarget
Jitendra Thakur, Steven Henikoff
We combined classical salt fractionation with chromatin immunoprecipitation to recover human centromeric chromatin under native conditions. We found that >85% of the total centromeric chromatin is insoluble under conditions typically used for native chromatin extraction. To map both soluble and insoluble chromatin in situ, we combined CUT&RUN (cleavage under targets and release using nuclease), a targeted nuclease method, with salt fractionation. Using this approach, we observed unexpected structural and conformational variations of centromere protein A (CENP-A)-containing complexes on different α-satellite dimeric units within highly homogenous arrays...
January 1, 2018: Genes & Development
Marvin J Fritzler, Marie Hudson, May Y Choi, Michael Mahler, Mianbo Wang, Chelsea Bentow, Jay Milo, Murray Baron
We studied the clinical correlations and epitopes of autoantibodies directed to a novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed its relationship to centromere protein A (CENP-A). 451 SSc sera were tested for anti-BICD2 using a paramagnetic bead immunoassay and then univariate and multivariate logistic regression was used to study the association between anti-BICD2 and demographic and clinical parameters as well as other SSc-related autoantibodies. Epitope mapping was performed on solid phase matrices...
January 21, 2018: Autoimmunity Reviews
Sivakanthan Kasinathan, Steven Henikoff
Animal and plant centromeres are embedded in repetitive "satellite" DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in < 10-bp dyad symmetries predicted to adopt non-B-form conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequence-specific DNA binding proteins with DNA bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B-form DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically non-essential...
January 22, 2018: Molecular Biology and Evolution
Tian Tian, Xiaorun Li, Yingying Liu, Chengliang Wang, Xing Liu, Guoqiang Bi, Xuan Zhang, Xuebiao Yao, Z Hong Zhou, Jianye Zang
No abstract text is available yet for this article.
January 19, 2018: Cell Research
Shengya Cao, Keda Zhou, Zhening Zhang, Karolin Luger, Aaron F Straight
Eukaryotic centromeres are defined by the presence of nucleosomes containing the histone H3 variant, Centromere Protein A (CENP-A). Once incorporated at centromeres, CENP-A nucleosomes are remarkably stable, exhibiting no detectable loss or exchange over many cell cycles. It is currently unclear whether this stability is an intrinsic property of CENP-A containing chromatin or whether it arises from proteins that specifically associate with CENP-A chromatin. Two proteins, CENP-C and CENP-N, are known to bind CENP-A human nucleosomes directly...
January 17, 2018: Molecular Biology of the Cell
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