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https://www.readbyqxmd.com/read/27911702/the-unconventional-kinetoplastid-kinetochore-from-discovery-toward-functional-understanding
#1
REVIEW
Bungo Akiyoshi
The kinetochore is the macromolecular protein complex that drives chromosome segregation in eukaryotes. Its most fundamental function is to connect centromeric DNA to dynamic spindle microtubules. Studies in popular model eukaryotes have shown that centromere protein (CENP)-A is critical for DNA-binding, whereas the Ndc80 complex is essential for microtubule-binding. Given their conservation in diverse eukaryotes, it was widely believed that all eukaryotes would utilize these components to make up a core of the kinetochore...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27893298/replication-checkpoint-suppression-and-structure-of-centromeric-dna
#2
Francesco Romeo, Lucia Falbo, Vincenzo Costanzo
Human centromeres contain large amounts of repetitive DNA sequences known as α satellite DNA, which can be difficult to replicate and whose functional role is unclear. Recently, we have characterized protein composition, structural organization and checkpoint response to stalled replication forks of centromeric chromatin reconstituted in Xenopus laevis egg extract. We showed that centromeric DNA has high affinity for SMC2-4 subunits of condensins and for CENP-A, it is enriched for DNA repair factors and suppresses the ATR checkpoint to ensure its efficient replication...
November 28, 2016: Nucleus
https://www.readbyqxmd.com/read/27880912/cenp-a-is-dispensable-for-mitotic-centromere-function-after-initial-centromere-kinetochore-assembly
#3
Sebastian Hoffmann, Marie Dumont, Viviana Barra, Peter Ly, Yael Nechemia-Arbely, Moira A McMahon, Solène Hervé, Don W Cleveland, Daniele Fachinetti
Human centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27858158/structure-of-centromere-chromatin-from-nucleosome-to-chromosomal-architecture
#4
REVIEW
Thomas Schalch, Florian A Steiner
The centromere is essential for the segregation of chromosomes, as it serves as attachment site for microtubules to mediate chromosome segregation during mitosis and meiosis. In most organisms, the centromere is restricted to one chromosomal region that appears as primary constriction on the condensed chromosome and is partitioned into two chromatin domains: The centromere core is characterized by the centromere-specific histone H3 variant CENP-A (also called cenH3) and is required for specifying the centromere and for building the kinetochore complex during mitosis...
November 17, 2016: Chromosoma
https://www.readbyqxmd.com/read/27820823/cenp-a-and-h3-nucleosomes-display-a-similar-stability-to-force-mediated-disassembly
#5
Sung Hyun Kim, Rifka Vlijm, Jaco van der Torre, Yamini Dalal, Cees Dekker
Centromere-specific nucleosomes are a central feature of the kinetochore complex during mitosis, in which microtubules exert pulling and pushing forces upon the centromere. CENP-A nucleosomes have been assumed to be structurally unique, thereby providing resilience under tension relative to their H3 canonical counterparts. Here, we directly test this hypothesis by subjecting CENP-A and H3 octameric nucleosomes, assembled on random or on centromeric DNA sequences, to varying amounts of applied force by using single-molecule magnetic tweezers...
2016: PloS One
https://www.readbyqxmd.com/read/27811920/acetylation-of-histone-h4-lysine-5-and-12-is-required-for-cenp-a-deposition-into-centromeres
#6
Wei-Hao Shang, Tetsuya Hori, Frederick G Westhorpe, Kristina M Godek, Atsushi Toyoda, Sadahiko Misu, Norikazu Monma, Kazuho Ikeo, Christopher W Carroll, Yasunari Takami, Asao Fujiyama, Hiroshi Kimura, Aaron F Straight, Tatsuo Fukagawa
Centromeres are specified epigenetically through the deposition of the centromere-specific histone H3 variant CENP-A. However, how additional epigenetic features are involved in centromere specification is unknown. Here, we find that histone H4 Lys5 and Lys12 acetylation (H4K5ac and H4K12ac) primarily occur within the pre-nucleosomal CENP-A-H4-HJURP (CENP-A chaperone) complex, before centromere deposition. We show that H4K5ac and H4K12ac are mediated by the RbAp46/48-Hat1 complex and that RbAp48-deficient DT40 cells fail to recruit HJURP to centromeres and do not incorporate new CENP-A at centromeres...
November 4, 2016: Nature Communications
https://www.readbyqxmd.com/read/27807043/hjurp-interaction-with-the-condensin-ii-complex-during-g1-promotes-cenp-a-deposition
#7
Meghan C Barnhart-Dailey, Prasad Trivedi, P Todd Stukenberg, Daniel R Foltz
Centromeric chromatin is required for kinetochore assembly during mitosis and accurate chromosome segregation. A unique nucleosome containing the histone H3-specific variant CENP-A is the defining feature of centromeric chromatin. In humans, CENP-A nucleosome deposition occurs in early G1 just following mitotic exit at the time when the CENP-A deposition machinery localizes to centromeres. The mechanism by which CENP-A is deposited onto an existing, condensed chromatin template is not understood. Here, we identify the selective association of the CENP-A chaperone HJURP with the condensin II complex and not condensin I...
November 2, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27794026/histone-h4-facilitates-the-proteolysis-of-the-budding-yeast-cenp-acse4-centromeric-histone-variant
#8
Gary M R Deyter, Erica M Hildebrand, Adrienne D Barber, Sue Biggins
The incorporation of histone variants into nucleosomes can alter chromatin-based processes. CENP-A is the histone H3 variant found exclusively at centromeres that serves as an epigenetic mark for centromere identity and is required for kinetochore assembly. CENP-A mislocalization to ectopic sites appears to contribute to genomic instability, transcriptional misregulation, and tumorigenesis, so mechanisms exist to ensure its exclusive localization to centromeres. One conserved process is proteolysis, which is mediated by the Psh1 E3 ubiquitin ligase in Saccharomyces cerevisiae (budding yeast)...
October 28, 2016: Genetics
https://www.readbyqxmd.com/read/27716277/array-cgh-diagnosis-in-ovarian-failure-identification-of-new-molecular-actors-for-ovarian-physiology
#9
Sylvie Jaillard, Linda Akloul, Marion Beaumont, Houda Hamdi-Roze, Christele Dubourg, Sylvie Odent, Solène Duros, Nathalie Dejucq-Rainsford, Marc-Antoine Belaud-Rotureau, Célia Ravel
BACKGROUND: Ovarian failure (OF) is considered premature if it occurs before the age of 40. This study investigates the genetic aetiology underlying OF in women under the age of 40 years. METHODS: We conducted an experimental prospective study performing all genome microarrays in 60 patients younger than 40 years presenting an OF revealed by a decrease of circulating Anti-Müllerian Hormone (AMH) and leading to an oocyte donation program. RESULTS: We identified nine significant copy number variations (CNVs) including candidate genes potentially implicated in reproductive function...
October 3, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27696824/maintenance-and-function-of-a-plant-chromosome-in-human-cells
#10
Naoki Wada, Yasuhiro Kazuki, Kanako Kazuki, Toshiaki Inoue, Kiichi Fukui, Mitsuo Oshimura
Replication, segregation, gene expression and inheritance are essential features of all eukaryotic chromosomes. To delineate the extent of conservation of chromosome functions between humans and plants during evolutionary history, we have generated the first human cell line containing an Arabidopsis chromosome. The Arabidopsis chromosome was mitotically stable in hybrid cells following cell division, and initially existed as a translocated chromosome. During culture, the translocated chromosomes then converted to two types of independent plant chromosomes without human DNA sequences, with the reproducibility...
October 4, 2016: ACS Synthetic Biology
https://www.readbyqxmd.com/read/27670610/skin-specific-deletion-of-mis18%C3%AE-impedes-proliferation-and-stratification-of-epidermal-keratinocytes
#11
Koog Chan Park, Minkyoung Lee, Yoon Jeon, Raok Jeon, Sung Hee Baek, Ho Lee, Keun Il Kim
The Mis18 proteins (Mis18α, Mis18β and M18BP1) are pivotal to the deposition of CENP-A at the centromere during cell cycle progression and are indispensable for embryonic development. Here, we show that Mis18α is critical for the proliferation of keratinocytes and stratification of the epidermis. Mice lacking Mis18α in the epidermis died shortly after birth, showing skin abnormalities like thin and translucent skin as well as defective skin barrier functions. The epidermis of newborn Mis18α-deficient mice lacked distinct stratification and mature hair follicles, with a reduction in the number of proliferating cells and increased cell death in the basal layer...
September 23, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27666591/ccp1-homodimer-mediates-chromatin-integrity-by-antagonizing-cenp-a-loading
#12
Qianhua Dong, Feng-Xiang Yin, Feng Gao, Yuan Shen, Faben Zhang, Yang Li, Haijin He, Marlyn Gonzalez, Jinpu Yang, Shu Zhang, Min Su, Yu-Hang Chen, Fei Li
CENP-A is a centromere-specific histone 3 variant essential for centromere specification. CENP-A partially replaces canonical histone H3 at the centromeres. How the particular CENP-A/H3 ratio at centromeres is precisely maintained is unknown. It also remains unclear how CENP-A is excluded from non-centromeric chromatin. Here, we identify Ccp1, an uncharacterized NAP family protein in fission yeast that antagonizes CENP-A loading at both centromeric and non-centromeric regions. Like the CENP-A loading factor HJURP, Ccp1 interacts with CENP-A and is recruited to centromeres at the end of mitosis in a Mis16-dependent manner...
October 6, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27652331/the-inheritance-of-centromere-identity
#13
Yohei Niikura, Risa Kitagawa, Katsumi Kitagawa
CENP-A (Centromere protein A) is a histone H3 variant that epigenetically determines the centromere position, but the mechanism of its centromere inheritance is obscure. We propose that CENP-A ubiquitylation, which is inherited through dimerization between rounds of cell division, is a candidate for the epigenetic mark of centromere identity.
July 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27581771/human-centromere-repositioning-within-euchromatin-after-partial-chromosome-deletion
#14
Lori L Sullivan, Kristin A Maloney, Aaron J Towers, Simon G Gregory, Beth A Sullivan
Centromeres are defined by a specialized chromatin organization that includes nucleosomes that contain the centromeric histone variant centromere protein A (CENP-A) instead of canonical histone H3. Studies in various organisms have shown that centromeric chromatin (i.e., CENP-A chromatin or centrochromatin) exhibits plasticity, in that it can assemble on different types of DNA sequences. However, once established on a chromosome, the centromere is maintained at the same position. In humans, this location is the highly homogeneous repetitive DNA alpha satellite...
August 31, 2016: Chromosome Research
https://www.readbyqxmd.com/read/27580032/insights-from-biochemical-reconstitution-into-the-architecture-of-human-kinetochores
#15
John R Weir, Alex C Faesen, Kerstin Klare, Arsen Petrovic, Federica Basilico, Josef Fischböck, Satyakrishna Pentakota, Jenny Keller, Marion E Pesenti, Dongqing Pan, Doro Vogt, Sabine Wohlgemuth, Franz Herzog, Andrea Musacchio
Chromosomes are carriers of genetic material and their accurate transfer from a mother cell to its two daughters during cell division is of paramount importance for life. Kinetochores are crucial for this process, as they connect chromosomes with microtubules in the mitotic spindle. Kinetochores are multi-subunit complexes that assemble on specialized chromatin domains, the centromeres, that are able to enrich nucleosomes containing the histone H3 variant centromeric protein A (CENP-A). A group of several additional CENPs, collectively known as constitutive centromere associated network (CCAN), establish the inner kinetochore, whereas a ten-subunit assembly known as the KMN network creates a microtubule-binding site in the outer kinetochore...
August 31, 2016: Nature
https://www.readbyqxmd.com/read/27545882/differential-chromosomal-localization-of-centromeric-histone-cenp-a-contributes-to-nematode-programmed-dna-elimination
#16
Yuanyuan Kang, Jianbin Wang, Ashley Neff, Stella Kratzer, Hiroshi Kimura, Richard E Davis
The stability of the genome is paramount to organisms. However, diverse eukaryotes carry out programmed DNA elimination in which portions or entire chromsomes are lost in early development or during sex determination. During early development of the parasitic nematode, Ascaris suum, 13% of the genome is eliminated. How different genomic segments are reproducibly retained or discarded is unknown. Here, we show that centromeric histone CENP-A localization plays a key role in this process. We show that Ascaris chromosomes are holocentric during germline mitoses, with CENP-A distributed along their length...
August 30, 2016: Cell Reports
https://www.readbyqxmd.com/read/27524485/ccan-assembly-configures-composite-binding-interfaces-to-promote-cross-linking-of-ndc80-complexes-at-the-kinetochore
#17
Gülsah Pekgöz Altunkaya, Francesca Malvezzi, Zuzana Demianova, Tomasz Zimniak, Gabriele Litos, Florian Weissmann, Karl Mechtler, Franz Herzog, Stefan Westermann
Partitioning of the genome requires kinetochores, large protein complexes that mediate dynamic attachment of chromosomes to the spindle. Kinetochores contain two supramolecular protein assemblies. The ten-protein KMN network harbors key microtubule-binding sites in the Ndc80 complex and mediates assembly of checkpoint complexes via the KNL-1/Spc105 protein [1, 2]. As KMN does not contact DNA directly, it relies on different centromere-binding proteins for recruitment and cell-cycle-dependent assembly. These proteins are collectively referred to as the CCAN (constitutive centromere-associated network) [2-4]...
September 12, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27499292/the-flexible-ends-of-cenp-a-nucleosome-are-required-for-mitotic-fidelity
#18
Yohan Roulland, Khalid Ouararhni, Mladen Naidenov, Lorrie Ramos, Muhammad Shuaib, Sajad Hussain Syed, Imtiaz Nizar Lone, Ramachandran Boopathi, Emeline Fontaine, Gabor Papai, Hiroaki Tachiwana, Thierry Gautier, Dimitrios Skoufias, Kiran Padmanabhan, Jan Bednar, Hitoshi Kurumizaka, Patrick Schultz, Dimitar Angelov, Ali Hamiche, Stefan Dimitrov
CENP-A is a histone variant, which replaces histone H3 at centromeres and confers unique properties to centromeric chromatin. The crystal structure of CENP-A nucleosome suggests flexible nucleosomal DNA ends, but their dynamics in solution remains elusive and their implication in centromere function is unknown. Using electron cryo-microscopy, we determined the dynamic solution properties of the CENP-A nucleosome. Our biochemical, proteomic, and genetic data reveal that higher flexibility of DNA ends impairs histone H1 binding to the CENP-A nucleosome...
August 18, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27454815/promiscuous-histone-mis-assembly-is-actively-prevented-by-chaperones
#19
Haiqing Zhao, David Winogradoff, Minh Bui, Yamini Dalal, Garegin A Papoian
Histone proteins are essential for the organization, expression, and inheritance of genetic material for eukaryotic cells. A centromere-specific H3 histone variant, centromere protein A (CENP-A), shares about 50% amino acid sequence identity with H3. CENP-A is required for packaging the centromere and for the proper separation of chromosomes during mitosis. Despite their distinct biological functions, previously reported crystal structures of the CENP-A/H4 and H3/H4 dimers reveal a high degree of similarity...
October 12, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27449713/formin-mediated-epigenetic-maintenance-of-centromere-identity
#20
Chenshu Liu, Yinghui Mao
Accurate chromosome segregation in mammalian cells is guided by the centromere, a specialized chromosome region defined by the histone H3 variant centromere protein A (CENP-A). It is not well understood how cells maintain CENP-A levels at centromeres while continuously going through genome replications and cell divisions. A MgcRacGAP-dependent small GTPase molecular switch has been shown as essential for centromeric CENP-A maintenance. By using quantitative imaging, pulse-chase and live cell analysis, a recent work has suggested that the diaphanous formin mDia2, a well-established small GTPase effector, functions downstream of this small GTPase pathway to maintain CENP-A levels at centromeres...
July 22, 2016: Small GTPases
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