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https://www.readbyqxmd.com/read/28334768/repair-of-uv-induced-dna-lesions-in-natural-saccharomyces-cerevisiae-telomeres-is-moderated-by-sir2-and-sir3-and-inhibited-by-yku-sir4-interaction
#1
Laetitia Guintini, Maxime Tremblay, Martin Toussaint, Annie D'Amours, Ralf E Wellinger, Raymund J Wellinger, Antonio Conconi
Ultraviolet light (UV) causes DNA damage that is removed by nucleotide excision repair (NER). UV-induced DNA lesions must be recognized and repaired in nucleosomal DNA, higher order structures of chromatin and within different nuclear sub-compartments. Telomeric DNA is made of short tandem repeats located at the ends of chromosomes and their maintenance is critical to prevent genome instability. In Saccharomyces cerevisiae the chromatin structure of natural telomeres is distinctive and contingent to telomeric DNA sequences...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28333638/a-comparative-study-for-identifying-the-chromosome-wide-spatial-clusters-from-high-throughput-chromatin-conformation-capture-data
#2
Xiangtao Li, Ka-Chun Wong
In the past years, the high-throughput sequencing technologies have enabled massive insights into genomic annotations. In contrast, the full-scale three-dimensional arrangements of genomic regions are relatively unknown. Thanks to the recent breakthroughs in High-throughput Chromosome Conformation Capture (Hi-C) techniques, non-negative matrix factorization (NMF) has been adopted to identify local spatial clusters of genomic regions from Hi-C data. However, such non-negative matrix factorization entails a high-dimensional non-convex objective function to be optimized with non-negative constraints...
March 20, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28333241/dysmorphic-patterns-are-associated-with-cytoskeletal-alterations-in-human-oocytes
#3
Mariabeatrice Dal Canto, Maria Cristina Guglielmo, Mario Mignini Renzini, Rubens Fadini, Clarissa Moutier, Maria Merola, Elena De Ponti, Giovanni Coticchio
Study Question: Are specific morphological anomalies in human mature oocytes, as revealed by transmitted light microscopy, associated with intrinsic damage to the meiotic spindle and actin cytoskeleton? SUMMARY ANSWER: Aggregates of smooth endoplasmic reticulum (SER) and domains of centrally localized granular cytoplasm (GC) reflect intrinsic damage to the oocyte cytoskeleton, namely alterations in spindle size, chromosome misalignment and cortical actin disorganization...
March 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28329763/the-allosteric-inhibitor-abl001-enables-dual-targeting-of-bcr-abl1
#4
Andrew A Wylie, Joseph Schoepfer, Wolfgang Jahnke, Sandra W Cowan-Jacob, Alice Loo, Pascal Furet, Andreas L Marzinzik, Xavier Pelle, Jerry Donovan, Wenjing Zhu, Silvia Buonamici, A Quamrul Hassan, Franco Lombardo, Varsha Iyer, Michael Palmer, Giuliano Berellini, Stephanie Dodd, Sanjeev Thohan, Hans Bitter, Susan Branford, David M Ross, Timothy P Hughes, Lilli Petruzzelli, K Gary Vanasse, Markus Warmuth, Francesco Hofmann, Nicholas J Keen, William R Sellers
Chronic myeloid leukaemia (CML) is driven by the activity of the BCR-ABL1 fusion oncoprotein. ABL1 kinase inhibitors have improved the clinical outcomes for patients with CML, with over 80% of patients treated with imatinib surviving for more than 10 years. Second-generation ABL1 kinase inhibitors induce more potent molecular responses in both previously untreated and imatinib-resistant patients with CML. Studies in patients with chronic-phase CML have shown that around 50% of patients who achieve and maintain undetectable BCR-ABL1 transcript levels for at least 2 years remain disease-free after the withdrawal of treatment...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28326434/genetic-architecture-of-male-fertility-restoration-of-triticum-timopheevii-cytoplasm-and-fine-mapping-of-the-major-restorer-locus-rf3-on-chromosome-1b
#5
Tobias Würschum, Willmar L Leiser, Sigrid Weissmann, Hans Peter Maurer
Restoration of fertility in the cytoplasmic male sterility-inducing Triticum timopheevii cytoplasm can be achieved with the major restorer locus Rf3 located on chromosome 1B, but is also dependent on modifier loci. Hybrid breeding relies on a hybrid mechanism enabling a cost-efficient hybrid seed production. In wheat and triticale, cytoplasmic male sterility based on the T. timopheevii cytoplasm is commonly used, and the aim of this study was to dissect the genetic architecture underlying fertility restoration...
March 21, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/28324510/analysis-of-telomere-homologous-dna-with-different-conformations-using-2d-agarose-electrophoresis-and-in-gel-hybridization
#6
Zepeng Zhang, Qian Hu, Yong Zhao
In mammalian cells, in addition to double-stranded telomeric DNA at chromosome ends, extra telomere-homologous DNA is present that adopts different conformations, including single-stranded G- or C-rich DNA, extrachromosomal circular DNA (T-circle), and telomeric complex (T-complex) with an unidentified structure. The formation of such telomere-homologous DNA is closely related to telomeric DNA metabolism and chromosome end protection by telomeres. Conventional agarose gel electrophoresis is unable to separate DNA based on conformation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28320757/additional-candidate-genes-for-human-atherosclerotic-disease-identified-through-annotation-based-on-chromatin-organization
#7
Saskia Haitjema, Claartje A Meddens, Sander W van der Laan, Daniel Kofink, Magdalena Harakalova, Vinicius Tragante, Hassan Foroughi Asl, Jessica van Setten, Maarten M Brandt, Joshua C Bis, Christopher O'Donnell, Caroline Cheng, Imo E Hoefer, Johannes Waltenberger, Erik Biessen, J Wouter Jukema, Pieter A F M Doevendans, Edward E S Nieuwenhuis, Jeanette Erdmann, Johan L M Björkegren, Gerard Pasterkamp, Folkert W Asselbergs, Hester M den Ruijter, Michal Mokry
BACKGROUND: As genome-wide association efforts, such as CARDIoGRAM and METASTROKE, are ongoing to reveal susceptibility loci for their underlying disease-atherosclerotic disease-identification of candidate genes explaining the associations of these loci has proven the main challenge. Many disease susceptibility loci colocalize with DNA regulatory elements, which influence gene expression through chromatin interactions. Therefore, the target genes of these regulatory elements can be considered candidate genes...
April 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28289288/3d-structures-of-individual-mammalian-genomes-studied-by-single-cell-hi-c
#8
Tim J Stevens, David Lando, Srinjan Basu, Liam P Atkinson, Yang Cao, Steven F Lee, Martin Leeb, Kai J Wohlfahrt, Wayne Boucher, Aoife O'Shaughnessy-Kirwan, Julie Cramard, Andre J Faure, Meryem Ralser, Enrique Blanco, Lluis Morey, Miriam Sansó, Matthieu G S Palayret, Ben Lehner, Luciano Di Croce, Anton Wutz, Brian Hendrich, Dave Klenerman, Ernest D Laue
The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell...
March 13, 2017: Nature
https://www.readbyqxmd.com/read/28288562/genetic-diversity-and-signatures-of-selection-in-various-goat-breeds-revealed-by-genome-wide-snp-markers
#9
Luiz F Brito, James W Kijas, Ricardo V Ventura, Mehdi Sargolzaei, Laercio R Porto-Neto, Angela Cánovas, Zeny Feng, Mohsen Jafarikia, Flávio S Schenkel
BACKGROUND: The detection of signatures of selection has the potential to elucidate the identities of genes and mutations associated with phenotypic traits important for livestock species. It is also very relevant to investigate the levels of genetic diversity of a population, as genetic diversity represents the raw material essential for breeding and has practical implications for implementation of genomic selection. A total of 1151 animals from nine goat populations selected for different breeding goals and genotyped with the Illumina Goat 50K single nucleotide polymorphisms (SNP) Beadchip were included in this investigation...
March 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28286005/overall-shapes-of-the-smc-scpab-complex-are-determined-by-balance-between-constraint-and-relaxation-of-its-structural-parts
#10
Katsuhiko Kamada, Masayuki Su'etsugu, Hiraku Takada, Makoto Miyata, Tatsuya Hirano
The SMC-ScpAB complex plays a crucial role in chromosome organization and segregation in many bacteria. It is composed of a V-shaped SMC dimer and an ScpAB subcomplex that bridges the two Structural Maintenance of Chromosomes (SMC) head domains. Despite its functional significance, the mechanistic details of SMC-ScpAB remain obscure. Here we provide evidence that ATP-dependent head-head engagement induces a lever movement of the SMC neck region, which might help to separate juxtaposed coiled-coil arms. Binding of the ScpA N-terminal domain (NTD) to the SMC neck region is negatively regulated by the ScpB C-terminal domain...
March 7, 2017: Structure
https://www.readbyqxmd.com/read/28285903/prc2-facilitates-the-regulatory-topology-required-for-poised-enhancer-function-during-pluripotent-stem-cell-differentiation
#11
Sara Cruz-Molina, Patricia Respuela, Christina Tebartz, Petros Kolovos, Milos Nikolic, Raquel Fueyo, Wilfred F J van Ijcken, Frank Grosveld, Peter Frommolt, Hisham Bazzi, Alvaro Rada-Iglesias
Poised enhancers marked by H3K27me3 in pluripotent stem cells have been implicated in the establishment of somatic expression programs during embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Using CRISPR/Cas9 technology to engineer precise genetic deletions, we demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Interestingly, circularized chromosome conformation capture sequencing (4C-seq) shows that poised enhancers already establish physical interactions with their target genes in ESCs in a polycomb repressive complex 2 (PRC2)-dependent manner...
February 28, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28284913/higher-order-assembly-folding-the-chromosome
#12
REVIEW
Sven A Sewitz, Zahra Fahmi, Karen Lipkow
The linear molecules of DNA that constitute a eukaryotic genome have to be carefully organised within the nucleus to be able to correctly direct gene expression. Microscopy and chromosome capture methods have revealed a hierarchical organisation into territories, domains and subdomains that ensure the accessibility of expressed genes and eventually chromatin loops that serve to bring gene enhancers into proximity of their target promoters. A rapidly growing number of genome-wide datasets and their analyses have given detailed information into the conformation of the entire genome, allowing evolutionary insights, observations of genome rearrangements during development and the identification of new gene-to-disease associations...
March 8, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28263325/genome-wide-mapping-of-long-range-contacts-unveils-clustering-of-dna-double-strand-breaks-at-damaged-active-genes
#13
François Aymard, Marion Aguirrebengoa, Emmanuelle Guillou, Biola M Javierre, Beatrix Bugler, Coline Arnould, Vincent Rocher, Jason S Iacovoni, Anna Biernacka, Magdalena Skrzypczak, Krzysztof Ginalski, Maga Rowicka, Peter Fraser, Gaëlle Legube
The ability of DNA double-strand breaks (DSBs) to cluster in mammalian cells has been a subject of intense debate in recent years. Here we used a high-throughput chromosome conformation capture assay (capture Hi-C) to investigate clustering of DSBs induced at defined loci in the human genome. The results unambiguously demonstrated that DSBs cluster, but only when they are induced within transcriptionally active genes. Clustering of damaged genes occurs primarily during the G1 cell-cycle phase and coincides with delayed repair...
March 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28263316/single-molecule-sequencing-and-chromatin-conformation-capture-enable-de-novo-reference-assembly-of-the-domestic-goat-genome
#14
Derek M Bickhart, Benjamin D Rosen, Sergey Koren, Brian L Sayre, Alex R Hastie, Saki Chan, Joyce Lee, Ernest T Lam, Ivan Liachko, Shawn T Sullivan, Joshua N Burton, Heather J Huson, John C Nystrom, Christy M Kelley, Jana L Hutchison, Yang Zhou, Jiajie Sun, Alessandra Crisà, F Abel Ponce de León, John C Schwartz, John A Hammond, Geoffrey C Waldbieser, Steven G Schroeder, George E Liu, Maitreya J Dunham, Jay Shendure, Tad S Sonstegard, Adam M Phillippy, Curtis P Van Tassell, Timothy P L Smith
The decrease in sequencing cost and increased sophistication of assembly algorithms for short-read platforms has resulted in a sharp increase in the number of species with genome assemblies. However, these assemblies are highly fragmented, with many gaps, ambiguities, and errors, impeding downstream applications. We demonstrate current state of the art for de novo assembly using the domestic goat (Capra hircus) based on long reads for contig formation, short reads for consensus validation, and scaffolding by optical and chromatin interaction mapping...
March 6, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28262192/evaluation-of-structural-factors-potentially-implicated-in-acute-lymphoblastic-leukemia-a-report-of-the-migiccl
#15
Dulce María López-Sánchez, Alfonso Méndez-Tenorio, Jorge Alberto Roacho-Pérez, Angélica Rangel-López
BACKGROUND AND AIMS: Acute lymphoblastic leukemia (ALL) is the most common cancer in the pediatric population; ∼80% of the cases show some translocation. Translocations that result in ALL are due to chromosome breaks. However, the exact mechanisms that cause these breaks have not been well studied. A detailed search of the breakpoints associated with ALL reported in the NCBI database shows that some are concentrated in limited regions of the chromosome, whereas others are scattered throughout...
October 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28258094/nucleome-analysis-reveals-structure-function-relationships-for-colon-cancer
#16
Laura Seaman, Haiming Chen, Markus Brown, Darawalee Wangsa, Geoff Patterson, Jordi Camps, Gilbert S Omenn, Thomas Ried, Indika Rajapakse
Chromosomal translocations and aneuploidy are hallmarks of cancer genomes; however, the impact of these aberrations on the nucleome (i.e., nuclear structure and gene expression) are not yet understood. Here, the nucleome of the colorectal cancer cell line HT-29 was analyzed using chromosome conformation capture (Hi-C) to study genome structure, complemented by RNA sequencing (RNA-seq) to determine consequent changes in genome function. Importantly, translocations and copy number changes were identified at high resolution from Hi-C data and the structure-function relationships present in normal cells were maintained in cancer...
March 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28257137/novel-players-in-x-inactivation-insights-into-xist-mediated-gene-silencing-and-chromosome-conformation
#17
REVIEW
Simão T da Rocha, Edith Heard
The nuclear long noncoding RNA (lncRNA) Xist ensures X-chromosome inactivation (XCI) in female placental mammals. Although Xist is one of the most intensively studied lncRNAs, the mechanisms associated with its capacity to trigger chromosome-wide gene silencing, the formation of facultative heterochromatin and an unusual 3D conformation of the inactive X chromosome (Xi) have remained elusive. Now researchers have identified novel functional partners of Xist in a series of breakthrough studies, using unbiased techniques to isolate Xist-bound proteins, as well as forward genetic screens...
March 3, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28251841/topologically-associated-domains-a-successful-scaffold-for-the-evolution-of-gene-regulation-in-animals
#18
REVIEW
Rafael D Acemel, Ignacio Maeso, José Luis Gómez-Skarmeta
The evolution of gene regulation is considered one of the main drivers causing the astonishing morphological diversity in the animal kingdom. Gene regulation in animals heavily depends upon cis-regulatory elements, discrete pieces of DNA that interact with target promoters to regulate gene expression. In the last years, Chromosome Conformation Capture experiments (4C-seq, 5C, and HiC) in several organisms have shown that the genomes of many bilaterian animals are organized in the 3D chromatin space in compartments called topologically associated domains (TADs)...
March 2, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28242723/resolution-of-mismatched-overlap-holliday-junction-intermediates-by-the-tyrosine-recombinase-intdot
#19
Kenneth Ringwald, Sumiko Yoneji, Jeffrey Gardner
CTnDOT is an integrated conjugative element found in Bacteroides species. CTnDOT encodes for and transfers antibiotic resistance genes. The element integrates into and excises from the host chromosome via a Holliday junction intermediate as part of a site-specific recombination mechanism. The CTnDOT integrase, IntDOT, is a tyrosine recombinase with core-binding, catalytic and amino terminal domains. Unlike well-studied tyrosine recombinases such as lambda Int, IntDOT is able to resolve Holliday junctions containing heterology (mismatched bases) between the sites of strand exchange...
February 27, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28237780/computer-evaluation-of-vire2-protein-complexes-for-ssdna-transfer-ability
#20
Irina Volokhina, Yury Gusev, Svyatoslav Mazilov, Yelizaveta Moiseeva, Mikhail Chumakov
The single-stranded transfer DNA from the Ti plasmid of the soil bacteria Agrobacterium nonspecifically integrates into the plant chromosome and is inherited at subsequent cell divisions. How it is transferred across host membranes is unknown, but it is believed that VirE2 proteins form a membrane-spanning pore or channel in a lipid bilayer and possibly mediate the delivery of the single-stranded transfer DNA-VirD2-VirE2 complex to the plant cell chromosomes. The aim of this work was to perform a computer simulation of VirE2's pore-forming capacity and an evaluation of constructed VirE2 complexes...
February 9, 2017: Computational Biology and Chemistry
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