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Centromere protein

Motoko Unoki, Hironori Funabiki, Guillaume Velasco, Claire Francastel, Hiroyuki Sasaki
Mutations in CDCA7 and HELLS that respectively encode a CXXC-type zinc finger protein and a SNF2 family chromatin remodeler cause immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome type 3 and 4, respectively. Here, we demonstrate that classical non-homologous end joining (C-NHEJ) proteins Ku80 and Ku70, as well as HELLS coimmunoprecipitated with CDCA7. The coimmunoprecipitation of the repair proteins was sensitive to nuclease treatment and an ICF3 mutation in CDCA7 that impairs its chromatin binding...
October 11, 2018: Journal of Clinical Investigation
Adam Ameur, Huiwen Che, Marcel Martin, Ignas Bunikis, Johan Dahlberg, Ida Höijer, Susana Häggqvist, Francesco Vezzi, Jessica Nordlund, Pall Olason, Lars Feuk, Ulf Gyllensten
The current human reference sequence (GRCh38) is a foundation for large-scale sequencing projects. However, recent studies have suggested that GRCh38 may be incomplete and give a suboptimal representation of specific population groups. Here, we performed a de novo assembly of two Swedish genomes that revealed over 10 Mb of sequences absent from the human GRCh38 reference in each individual. Around 6 Mb of these novel sequences (NS) are shared with a Chinese personal genome. The NS are highly repetitive, have an elevated GC-content, and are primarily located in centromeric or telomeric regions...
October 9, 2018: Genes
Ewelina Zasadzińska, Jiehuan Huang, Aaron O Bailey, Lucie Y Guo, Nancy S Lee, Shashank Srivastava, Kelvin A Wong, Bradley T French, Ben E Black, Daniel R Foltz
Centromeric chromatin defines the site of kinetochore formation and ensures faithful chromosome segregation. Centromeric identity is epigenetically specified by the incorporation of CENP-A nucleosomes. DNA replication presents a challenge for inheritance of centromeric identity because nucleosomes are removed to allow for replication fork progression. Despite this challenge, CENP-A nucleosomes are stably retained through S phase. We used BioID to identify proteins transiently associated with CENP-A during DNA replication...
October 3, 2018: Developmental Cell
Tisha Bohr, Christian R Nelson, Stefani Giacopazzi, Piero Lamelza, Needhi Bhalla
The conserved factor Shugoshin is dispensable in C. elegans for the two-step loss of sister chromatid cohesion that directs the proper segregation of meiotic chromosomes. We show that the C. elegans ortholog of Shugoshin, SGO-1, is required for checkpoint activity in meiotic prophase. This role in checkpoint function is similar to that of conserved proteins that structure meiotic chromosome axes. Indeed, null sgo-1 mutants exhibit additional phenotypes similar to that of a partial loss-of-function allele of the axis component, HTP-3: premature synaptonemal complex disassembly, the activation of alternate DNA repair pathways, and an inability to recruit a conserved effector of the DNA damage pathway, HUS-1...
October 1, 2018: Current Biology: CB
Jean-Benoît Le Luduec, Anupa Kudva, Jeanette E Boudreau, Katharine C Hsu
Allelic diversity of the KIR2DL receptors drive differential expression and ligand-binding affinities that impact natural killer cell function and patient outcomes for diverse cancers. We have developed a global intermediate resolution amplification-refractory mutation system (ARMS) PCR-SSP method for distinguishing functionally relevant subgroups of the KIR2DL receptors, as defined by phylogenetic study of the protein sequences. Use of the ARMS design makes the method reliable and usable as a kit, with all reactions utilizing the same conditions...
October 5, 2018: Scientific Reports
Zhigang Wu, Dongming Fang, Rui Yang, Fei Gao, Xingyu An, Xiaoxuan Zhuo, Yafei Li, Chuandeng Yi, Tao Zhang, Chengzhi Liang, Peng Cui, Zhukuan Cheng, Qiong Luo
The wild relatives of rice have adapted to different ecological environments and constitute a useful reservoir of agronomic traits for genetic improvement. Here we present the ~777 Mb de novo assembled genome sequence of Oryza granulata . Recent bursts of long-terminal repeat retrotransposons, especially RIRE2 , led to a rapid twofold increase in genome size after O. granulata speciation. Universal centromeric tandem repeats are absent within its centromeres, while gypsy -type LTRs constitute the main centromere-specific repetitive elements...
2018: Communications biology
Lorena Veneziano, Viviana Barra, Danilo Cilluffo, Aldo Di Leonardo
The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that ensures the fidelity of chromosomes segregation. Reduced expression of some of its components weakens the SAC and induces chromosome instability and aneuploidy, which are both well-known hallmarks of cancer cells. Centromere protein-E (CENP-E) is a crucial component of the SAC and its function is to facilitate kinetochore microtubule attachment required to achieve and maintain chromosome alignment. The present study investigates the possible role of p14ARF as a controller of aneuploid cells proliferation...
September 27, 2018: Molecular Genetics and Genomics: MGG
Hemant Kumar Prajapati, Meenakshi Agarwal, Priyanka Mittal, Santanu K Ghosh
Halving of the genome during meiosis I is achieved as the homologous chromosomes move to the opposite spindle poles whereas the sister chromatids stay together and move to the same pole. This requires that the sister kinetochores should take a side-by-side orientation in order to connect to the microtubules emanating from the same pole. Factors that constrain sister kinetochores to adopt such orientation are therefore crucial to achieve reductional chromosome segregation in meiosis I. In budding yeast, a protein complex, known as monopolin, is involved in conjoining of the sister kinetochores and thus facilitates their binding to the microtubules from the same pole...
September 25, 2018: G3: Genes—Genomes—Genetics
Elopy N Sibanda, Margo Chase-Topping, Lorraine T Pfavayi, Mark E J Woolhouse, Francisca Mutapi
Background: The autoimmune disease systemic lupus erythematosus (SLE) occurs more frequently in patients of African descent with high morbidity and mortality. Current SLE diagnostic criteria including antinuclear antibody (ANA) reactivity are derived largely from non-African populations. This study characterises ANA reactivity patterns and relates them to SLE clinical presentation in Black African patients. Methods: Sera from Black participants (61 patients with SLE and 100 controls) aged 1-81 years were analysed for reactivity against the antigens: uridine 1-ribonuclear protein, Smith uridine-1-5 ribonuclear protein antigen, soluble substance-A, recombinant Ro-52, soluble substance-B, Scl-70, cytoplasmic histidyl-tRNA synthetase antigen, proliferating cell nuclear antigen (PCNA), nucleosomes, ribonuclear P-protein, antimitochondrial antibody M2 (AMA-M2), histones, double-stranded DNA (dsDNA), centromere protein B and polymyositis-sclerosis overlap antigen...
2018: BMJ Global Health
Benoît Piégu, Peter Arensburger, Florian Guillou, Yves Bigot
The chicken genome was the third vertebrate to be sequenced. To date, its sequence and feature annotations are used as the reference for avian models in genome sequencing projects developed on birds and other Sauropsida species, and in genetic studies of domesticated birds of economic and evolutionary biology interest. Therefore, an accurate description of this genome model is important to a wide number of scientists. Here, we review the location and features of a very basic element, the centromeres of chromosomes in the galGal5 genome model...
September 17, 2018: Chromosome Research
Kata Sarlós, Andreas S Biebricher, Anna H Bizard, Julia A M Bakx, Anna G Ferreté-Bonastre, Mauro Modesti, Manikandan Paramasivam, Qi Yao, Erwin J G Peterman, Gijs J L Wuite, Ian D Hickson
Faithful chromosome segregation requires that the sister chromatids be disjoined completely. Defective disjunction can lead to the persistence of histone-free threads of DNA known as ultra-fine bridges (UFBs) that connect the separating sister DNA molecules during anaphase. UFBs arise at specific genomic loci and can only be visualized by detection of associated proteins such as PICH, BLM, topoisomerase IIIα, and RPA. However, it remains unknown how these proteins work together to promote UFB processing. We used a combination of ensemble biochemistry and new single-molecule assays to reconstitute key steps of UFB recognition and processing by these human proteins in vitro...
September 2018: Nature Structural & Molecular Biology
Nedenia Bonvino Stafuzza, Rafael Medeiros de Oliveira Silva, Elisa Peripolli, Luiz Antônio Framartino Bezerra, Raysildo Barbosa Lôbo, Cláudio de Ulhoa Magnabosco, Fernando A Di Croce, Jason B Osterstock, Danísio Prado Munari, Daniela A Lino Lourenco, Fernando Baldi
The causal mutation for polledness in Nelore (Bos taurus indicus) breed seems to have appeared first in Brazil in 1957. The expression of the polled trait is known to be ruled by a few groups of alleles in taurine breeds; however, the genetic basis of this trait in indicine cattle is still unclear. The aim of this study was to identify genomic regions associated with the hornless trait in a commercial Nelore population. A total of 107,294 animals had phenotypes recorded and 2,238 were genotyped/imputed for 777k SNP...
2018: PloS One
Arshad Mehmood, Stephanie I Jones, Peng Tao, Benjamin G Janesko
Orbitals and orbital overlap are important concepts in chemistry but are seldom incorporated into medicinal chemistry analyses of drug-target interactions. Our orbital overlap distance D(r) quantifies the size of the "test orbital" that best overlaps with a system's computed orbitals at point r. The overlap distance provides information about all of the occupied orbitals across a molecule, extending frontier orbital (Fukui) analysis and complementing widely used maps of the surface electrostatic potential...
September 12, 2018: Journal of Chemical Information and Modeling
Shirong Ma, Linni Fan, Yixiong Liu, Yingmei Wang, Kangjie Yu, Lifeng Wang, Na Fang, Fang Liu, Shuangping Guo, Zhe Wang
BACKGROUND: Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas. Previous studies have shown that MET protein overexpressed in MFS patients and can serve as a prognostic factor. The reasons for MET protein overexpression include amplification of the MET gene, which is located on chromosome 7q. Triggered by an index case harboring chromosome 7 polysomy rather than MET gene amplification in myxofibrosarcoma, we investigated chromosome 7 polysomy in more cases. METHODS: Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed in 30 MFS cases (including 2 epithelioid variant) to detect the expression of MET protein and gene status...
August 21, 2018: Diagnostic Pathology
Jackie Lang, Adrienne Barber, Sue Biggins
Chromosome segregation depends on the kinetochore, the machine that establishes force-bearing attachments between DNA and spindle microtubules. Kinetochores are formed every cell cycle via a highly regulated process that requires coordinated assembly of multiple subcomplexes on specialized chromatin. To elucidate the underlying mechanisms, we developed an assay to assemble kinetochores de novo using centromeric DNA and budding yeast extracts. Assembly is enhanced by mitotic phosphorylation of the Dsn1 kinetochore protein and generates kinetochores capable of binding microtubules...
August 17, 2018: ELife
Kohta Yoshida, Asano Ishikawa, Atsushi Toyoda, Shuji Shigenobu, Asao Fujiyama, Jun Kitano
Intragenomic conflict, the conflict of interest between different genomic regions within an individual, is proposed as a mechanism driving both the rapid evolution of heterochromatin-related proteins and the establishment of intrinsic genomic incompatibility between species. Although molecular studies of laboratory model organisms have demonstrated the link between heterochromatin evolution and hybrid abnormalities, we know little about their link in natural systems. Previously, we showed that F1 hybrids between the Japan Sea stickleback and the Pacific Ocean stickleback show hybrid male sterility and found a region responsible for hybrid male sterility on the X chromosome, but did not identify any candidate genes...
August 17, 2018: Molecular Ecology
Julie K Monda, Iain M Cheeseman
Accurate chromosome segregation critically depends on the formation of attachments between microtubule polymers and each sister chromatid. The kinetochore is the macromolecular complex that assembles at the centromere of each chromosome during mitosis and serves as the link between the DNA and the microtubules. In this Cell Science at a Glance article and accompanying poster, we discuss the activities and molecular players that are involved in generating kinetochore-microtubule attachments, including the initial stages of lateral kinetochore-microtubule interactions and maturation to stabilized end-on attachments...
August 16, 2018: Journal of Cell Science
Gabriel Keeble-Gagnère, Philippe Rigault, Josquin Tibbits, Raj Pasam, Matthew Hayden, Kerrie Forrest, Zeev Frenkel, Abraham Korol, B Emma Huang, Colin Cavanagh, Jen Taylor, Michael Abrouk, Andrew Sharpe, David Konkin, Pierre Sourdille, Benoît Darrier, Frédéric Choulet, Aurélien Bernard, Simone Rochfort, Adam Dimech, Nathan Watson-Haigh, Ute Baumann, Paul Eckermann, Delphine Fleury, Angela Juhasz, Sébastien Boisvert, Marc-Alexandre Nolin, Jaroslav Doležel, Hana Šimková, Helena Toegelová, Jan Šafář, Ming-Cheng Luo, Francisco Câmara, Matthias Pfeifer, Don Isdale, Johan Nyström-Persson, Iwgsc, Dal-Hoe Koo, Matthew Tinning, Dangqun Cui, Zhengang Ru, Rudi Appels
BACKGROUND: Numerous scaffold-level sequences for wheat are now being released and, in this context, we report on a strategy for improving the overall assembly to a level comparable to that of the human genome. RESULTS: Using chromosome 7A of wheat as a model, sequence-finished megabase-scale sections of this chromosome were established by combining a new independent assembly using a bacterial artificial chromosome (BAC)-based physical map, BAC pool paired-end sequencing, chromosome-arm-specific mate-pair sequencing and Bionano optical mapping with the International Wheat Genome Sequencing Consortium RefSeq v1...
August 17, 2018: Genome Biology
Shin-Ichiro Hiraga, Chandre Monerawela, Yuki Katou, Sophie Shaw, Kate Rm Clark, Katsuhiko Shirahige, Anne D Donaldson
Despite its evolutionarily conserved function in controlling DNA replication, the chromosomal binding sites of the budding yeast Rif1 protein are not well understood. Here, we analyse genome-wide binding of budding yeast Rif1 by chromatin immunoprecipitation, during G1 phase and in S phase with replication progressing normally or blocked by hydroxyurea. Rif1 associates strongly with telomeres through interaction with Rap1. By comparing genomic binding of wild-type Rif1 and truncated Rif1 lacking the Rap1-interaction domain, we identify hundreds of Rap1-dependent and Rap1-independent chromosome interaction sites...
September 2018: EMBO Reports
Shinsuke Aida, Junko Aida, Miho Naoi, Mai Kato, Yukio Tsuura, Ichiro Natsume, Kaiyo Takubo
We estimated the telomere lengths of neoplastic and non-neoplastic mesothelial cells and examined their correlation with asbestos exposure and the expression of markers of mesothelial malignancy. Cell blocks of pleural effusion obtained from 35 cases of non-neoplastic disease (NN), 12 cases of malignant mesothelioma (MM) and 12 cases of carcinomatous effusion due to lung adenocarcinoma (LA) were examined. Fifteen of the 35 NN cases had pleural plaques (NNpp+) suggestive of asbestos exposure, and the other 20 cases had no pleural plaques (NNpp-)...
September 2018: Pathology International
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