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CENP-A

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https://www.readbyqxmd.com/read/29432128/n-terminal-sumoylation-of-centromeric-histone-h3-variant-cse4-regulates-its-proteolysis-to-prevent-mislocalization-to-non-centromeric-chromatin
#1
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
https://www.readbyqxmd.com/read/29416714/mitosis-specific-phosphorylation-of-mis18%C3%AE-by-aurora-b-kinase-enhances-kinetochore-recruitment-of-polo-like-kinase-1
#2
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
https://www.readbyqxmd.com/read/29386331/unexpected-conformational-variations-of-the-human-centromeric-chromatin-complex
#3
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 31, 2018: Genes & Development
https://www.readbyqxmd.com/read/29369808/bicaudal-d2-is-a-novel-autoantibody-target-in-systemic-sclerosis-that-shares-a-key-epitope-with-cenp-a-but-has-a-distinct-clinical-phenotype
#4
REVIEW
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
https://www.readbyqxmd.com/read/29350209/molecular-basis-for-cenp-n-recognition-of-cenp-a-nucleosome-on-the-human-kinetochore
#5
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
https://www.readbyqxmd.com/read/29343552/constitutive-centromere-associated-network-contacts-confer-differential-stability-on-cenp-a-nucleosomes-in-vitro-and-in-the-cell
#6
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
https://www.readbyqxmd.com/read/29323636/an-optimized-method-for-3d-fluorescence-co-localization-applied-to-human-kinetochore-protein-architecture
#7
Aussie Suzuki, Sarah K Long, Edward D Salmon
Two-color fluorescence co-localization in 3D (three-dimension) has the potential to achieve accurate measurements at the nanometer length scale. Here, we optimized a 3D fluorescence co-localization method that uses mean values for chromatic aberration correction to yield the mean separation with ~10 nm accuracy between green and red fluorescently labeled protein epitopes within single human kinetochores. Accuracy depended critically on achieving small standard deviations in fluorescence centroid determination, chromatic aberration across the measurement field, and coverslip thickness...
January 11, 2018: ELife
https://www.readbyqxmd.com/read/29305387/simple-and-complex-centromeric-satellites-in-drosophila-sibling-species
#8
Paul Talbert, Sivakanthan Kasinathan, Steven Henikoff
Centromeres are the chromosomal sites of assembly for kinetochores, the protein complexes that attach to spindle fibers and mediate separation of chromosomes to daughter cells in mitosis and meiosis. In most multicellular organisms, centromeres comprise a single specific family of tandem repeats, often 100-400 bp in length, found on every chromosome, typically in one location within heterochromatin. Drosophila melanogaster is unusual in that the heterochromatin contains many families of mostly short (5-12 bp) tandem repeats, none of which appear to be present at all centromeres, and none of which are found only at centromeres...
January 5, 2018: Genetics
https://www.readbyqxmd.com/read/29280735/decoding-the-centromeric-nucleosome-through-cenp-n
#9
Satyakrishna Pentakota, Keda Zhou, Charlotte Smith, Stefano Maffini, Arsen Petrovic, Garry P Morgan, John R Weir, Ingrid R Vetter, Andrea Musacchio, Karolin Luger
Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A...
December 27, 2017: ELife
https://www.readbyqxmd.com/read/29212814/structural-basis-for-assembly-of-the-cbf3-kinetochore-complex
#10
Vera Leber, Andrea Nans, Martin R Singleton
Eukaryotic chromosomes contain a specialised region known as the centromere, which forms the platform for kinetochore assembly and microtubule attachment. The centromere is distinguished by the presence of nucleosomes containing the histone H3 variant, CENP-A. In budding yeast, centromere establishment begins with the recognition of a specific DNA sequence by the CBF3 complex. This in turn facilitates CENP-ACse4 nucleosome deposition and kinetochore assembly. Here, we describe a 3.6 Å single-particle cryo-EM reconstruction of the core CBF3 complex, incorporating the sequence-specific DNA-binding protein Cep3 together with regulatory subunits Ctf13 and Skp1...
December 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29208640/shaping-chromatin-in-the-nucleus-the-bricks-and-the-architects
#11
David Sitbon, Katrina Podsypanina, Tejas Yadav, Geneviève Almouzni
Chromatin organization in the nucleus provides a vast repertoire of information in addition to that encoded genetically. Understanding how this organization impacts genome stability and influences cell fate and tumorigenesis is an area of rapid progress. Considering the nucleosome, the fundamental unit of chromatin structure, the study of histone variants (the bricks) and their selective loading by histone chaperones (the architects) is particularly informative. Here, we report recent advances in understanding how relationships between histone variants and their chaperones contribute to tumorigenesis using cell lines and Xenopus development as model systems...
December 5, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29196559/remarkable-evolutionary-plasticity-of-centromeric-chromatin
#12
Steven Henikoff, Jitendra Thakur, Sivakanthan Kasinathan, Paul B Talbert
Centromeres were familiar to cell biologists in the late 19th century, but for most eukaryotes the basis for centromere specification has remained enigmatic. Much attention has been focused on the cenH3 (CENP-A) histone variant, which forms the foundation of the centromere. To investigate the DNA sequence requirements for centromere specification, we applied a variety of epigenomic approaches, which have revealed surprising diversity in centromeric chromatin properties. Whereas each point centromere of budding yeast is occupied by a single precisely positioned tetrameric nucleosome with one cenH3 molecule, the "regional" centromeres of fission yeast contain unphased presumably octameric nucleosomes with two cenH3s...
December 1, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29194511/prolyl-isomerization-of-the-cenp-a-n-terminus-regulates-centromeric-integrity-in-fission-yeast
#13
Hwei Ling Tan, Kim Kiat Lim, Qiaoyun Yang, Jing-Song Fan, Ahmed Mahmoud Mohammed Sayed, Liy Sim Low, Bingbing Ren, Teck Kwang Lim, Qingsong Lin, Yu-Keung Mok, Yih-Cherng Liou, Ee Sin Chen
Centromeric identity and chromosome segregation are determined by the precise centromeric targeting of CENP-A, the centromere-specific histone H3 variant. The significance of the amino-terminal domain (NTD) of CENP-A in this process remains unclear. Here, we assessed the functional significance of each residue within the NTD of CENP-A from Schizosaccharomyces pombe (SpCENP-A) and identified a proline-rich 'GRANT' (Genomic stability-Regulating site within CENP-A N-Terminus) motif that is important for CENP-A function...
November 29, 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/29119119/an-exploration-of-the-impact-of-anticentromere-antibody-on-early-stage-embryo
#15
Ying Ying, Xi Guo, Yiping Zhong, Canquan Zhou
Background: Previously, we found women with positive anticentromere antibody showed impaired potential of oocyte maturation and embryo cleavage; the possible mechanism behind this phenomenon was still unknown. Objective: Thus, the present study aimed to preliminarily explore whether ACA could penetrate into the living embryos and impair their developmental potential via in vitro coculture with mouse embryos. Methods: Mouse embryos were collected and used for in vitro culture with polyclonal anticentromere protein A (CENP-A) antibody; then, immunofluorescence assay was performed to determine the penetration of antibody into embryos, and embryo development potential was observed...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29074736/molecular-basis-of-cenp-c-association-with-the-cenp-a-nucleosome-at-yeast-centromeres
#16
Hua Xiao, Feng Wang, Jan Wisniewski, Alexey K Shaytan, Rodolfo Ghirlando, Peter C FitzGerald, Yingzi Huang, Debbie Wei, Shipeng Li, David Landsman, Anna R Panchenko, Carl Wu
Histone CENP-A-containing nucleosomes play an important role in nucleating kinetochores at centromeres for chromosome segregation. However, the molecular mechanisms by which CENP-A nucleosomes engage with kinetochore proteins are not well understood. Here, we report the finding of a new function for the budding yeast Cse4/CENP-A histone-fold domain interacting with inner kinetochore protein Mif2/CENP-C. Strikingly, we also discovered that AT-rich centromere DNA has an important role for Mif2 recruitment. Mif2 contacts one side of the nucleosome dyad, engaging with both Cse4 residues and AT-rich nucleosomal DNA...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29040671/nanoscale-dynamics-of-centromere-nucleosomes-and-the-critical-roles-of-cenp-a
#17
Micah P Stumme-Diers, Siddhartha Banerjee, Mohtadin Hashemi, Zhiqiang Sun, Yuri L Lyubchenko
In the absence of a functioning centromere, chromosome segregation becomes aberrant, leading to an increased rate of aneuploidy. The highly specific recognition of centromeres by kinetochores suggests that specific structural characteristics define this region, however, the structural details and mechanism underlying this recognition remains a matter of intense investigation. To address this, high-speed atomic force microscopy was used for direct visualization of the spontaneous dynamics of CENP-A nucleosomes at the sub-second time scale...
October 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28980868/exploring-the-role-of-cenp-a-ser18-phosphorylation-in-cin-and-tumorigenesis
#18
Weiguo Zhang, Gary H Karpen, Qing Zhang
Chromosome instability (CIN) contributes to the development of many cancer. In this paper, we summarize our recent finding that a novel pathway by which FBW7 loss promotes Centromere Protein A (CENP-A) phosphorylation on Serine 18 through Cyclin E1/CDK2, therefore promoting CIN and tumorigenesis. Our finding demonstrates the importance of CENP-A post-translational modification on modulating centromere and mitotic functions in cancer.
October 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28980861/budding-yeast-cenp-acse4-interacts-with-the-n-terminus-of-sgo1-and-regulates-its-association-with-centromeric-chromatin
#19
Prashant K Mishra, Kriti S Thapa, Panyue Chen, Suyu Wang, Tony R Hazbun, Munira A Basrai
Shugoshin is an evolutionarily conserved protein, which is involved in tension sensing on mitotic chromosomes, kinetochore biorientation, and protection of centromeric (CEN) cohesin for faithful chromosome segregation. Interaction of the C-terminus of Sgo1 with phosphorylated histone H2A regulates its association with CEN and pericentromeric (peri-CEN) chromatin, whereas mutations in histone H3 selectively compromise the association of Sgo1 with peri-CEN but not CEN chromatin. Given that histone H3 is absent from CEN and is replaced by a histone H3 variant CENP-ACse4, we investigated if CENP-ACse4 interacts with Sgo1 and promotes its association with the CEN chromatin...
October 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28916652/lsd1-mediated-epigenetic-reprogramming-drives-cenpe-expression-and-prostate-cancer-progression
#20
Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C Boutros, Cheryl H Arrowsmith, Felix Y Feng, Anthony M Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H He
Androgen receptor (AR) signaling is a key driver of prostate cancer, and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant prostate cancer (CRPC). Here, we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell-cycle genes, including CENPE, a centromere binding protein and mitotic kinesin...
October 15, 2017: Cancer Research
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