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https://www.readbyqxmd.com/read/28430577/synthetic-lethal-interaction-between-the-tumour-suppressor-stag2-and-its-paralog-stag1
#1
Lorena Benedetti, Matteo Cereda, LeeAnn Monteverde, Nikita Desai, Francesca D Ciccarelli
Cohesin is a multi-protein complex that tethers sister chromatids during mitosis and mediates DNA repair, genome compartmentalisation and regulation of gene expression. Cohesin subunits frequently acquire cancer loss-of-function alterations and act as tumour suppressors in several tumour types. This has led to increased interest in cohesin as potential target in anti-cancer therapy. Here we show that the loss-of-function of STAG2, a core component of cohesin and an emerging tumour suppressor, leads to synthetic dependency of mutated cancer cells on its paralog STAG1...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428255/nucleosome-nucleosome-interactions-via-histone-tails-and-linker-dna-regulate-nuclear-rigidity
#2
Yuta Shimamoto, Sachiko Tamura, Hiroshi Masumoto, Kazuhiro Maeshima
Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We addressed this in the present study by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28425213/genotype-phenotype-correlations-in-cornelia-de-lange-syndrome-behavioral-characteristics-and-changes-with-age
#3
Joanna Moss, Jessica Penhallow, Morad Ansari, Stephanie Barton, David Bourn, David R FitzPatrick, Judith Goodship, Peter Hammond, Catherine Roberts, Alice Welham, Chris Oliver
Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated with unusual facial features, limb abnormalities, a wide range of health conditions, and intellectual disability. Mutations in five genes that encode (SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex have been identified in up to 70% of individuals. Genetic cause remains unknown for a proportion of individuals. There is substantial heterogeneity in all aspects of CdLS but very little is known about what predicts phenotypic heterogeneity...
April 19, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28424523/cohesin-is-positioned-in-mammalian-genomes-by-transcription-ctcf-and-wapl
#4
Georg A Busslinger, Roman R Stocsits, Petra van der Lelij, Elin Axelsson, Antonio Tedeschi, Niels Galjart, Jan-Michael Peters
Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-range chromosomal cis-interactions. Cohesin is also present at these sites, but has been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites, according to this or other models, is unknown...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28417363/carbohydrate-depolymerization-by-intricate-cellulosomal-systems
#5
Johanna Stern, Lior Artzi, Sarah Moraïs, Carlos M G A Fontes, Edward A Bayer
Cellulosomes are multi-enzymatic nanomachines that have been fine-tuned through evolution to efficiently deconstruct plant biomass. Integration of cellulosomal components occurs via highly ordered protein-protein interactions between the various enzyme-borne dockerin modules and the multiple copies of the cohesin modules located on the scaffoldin subunit. Recently, designer cellulosome technology has been established to provide insights into the architectural role of catalytic (enzymatic) and structural (scaffoldin) cellulosomal constituents for the efficient degradation of plant cell wall polysaccharides...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28408976/when-tads-go-bad-chromatin-structure-and-nuclear-organisation-in-human-disease
#6
REVIEW
Vera B Kaiser, Colin A Semple
Chromatin in the interphase nucleus is organised as a hierarchical series of structural domains, including self-interacting domains called topologically associating domains (TADs). This arrangement is thought to bring enhancers into closer physical proximity with their target genes, which often are located hundreds of kilobases away in linear genomic distance. TADs are demarcated by boundary regions bound by architectural proteins, such as CTCF and cohesin, although much remains to be discovered about the structure and function of these domains...
2017: F1000Research
https://www.readbyqxmd.com/read/28408410/decreased-cohesin-in-the-brain-leads-to-defective-synapse-development-and-anxiety-related-behavior
#7
Yuki Fujita, Koji Masuda, Masashige Bando, Ryuichiro Nakato, Yuki Katou, Takashi Tanaka, Masahiro Nakayama, Keizo Takao, Tsuyoshi Miyakawa, Tatsunori Tanaka, Yukio Ago, Hitoshi Hashimoto, Katsuhiko Shirahige, Toshihide Yamashita
Abnormal epigenetic regulation can cause the nervous system to develop abnormally. Here, we sought to understand the mechanism by which this occurs by investigating the protein complex cohesin, which is considered to regulate gene expression and, when defective, is associated with higher-level brain dysfunction and the developmental disorder Cornelia de Lange syndrome (CdLS). We generated conditional Smc3-knockout mice and observed greater dendritic complexity and larger numbers of immature synapses in the cerebral cortex of Smc3(+/-) mice...
April 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28397800/erratum-structural-basis-of-eco1-mediated-cohesin-acetylation
#8
William C H Chao, Benjamin O Wade, Céline Bouchoux, Andrew W Jones, Andrew G Purkiss, Stefania Federico, Nicola O'Reilly, Ambrosius P Snijders, Frank Uhlmann, Martin R Singleton
No abstract text is available yet for this article.
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28389644/assembly-of-ruminococcus-flavefaciens-cellulosome-revealed-by-structures-of-two-cohesin-dockerin-complexes
#9
Pedro Bule, Victor D Alves, Vered Israeli-Ruimy, Ana L Carvalho, Luís M A Ferreira, Steven P Smith, Harry J Gilbert, Shabir Najmudin, Edward A Bayer, Carlos M G A Fontes
Cellulosomes are sophisticated multi-enzymatic nanomachines produced by anaerobes to effectively deconstruct plant structural carbohydrates. Cellulosome assembly involves the binding of enzyme-borne dockerins (Doc) to repeated cohesin (Coh) modules located in a non-catalytic scaffoldin. Docs appended to cellulosomal enzymes generally present two similar Coh-binding interfaces supporting a dual-binding mode, which may confer increased positional adjustment of the different complex components. Ruminococcus flavefaciens' cellulosome is assembled from a repertoire of 223 Doc-containing proteins classified into 6 groups...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28383696/the-lsh-hells-homolog-irc5-contributes-to-cohesin-association-with-chromatin-in-yeast
#10
Ireneusz Litwin, Tomasz Bakowski, Ewa Maciaszczyk-Dziubinska, Robert Wysocki
Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin...
April 5, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28382430/dna-topoisomerase-ii-modulates-acetyl-regulation-of-cohesin-mediated-chromosome-dynamics
#11
Su-Jiun Lin, Matthew J O'Connell
Cohesin is one of three multi-protein structural maintenance of chromosome (SMC) complexes that regulate eukaryotic chromosome dynamics. It forms a ring-shaped structure that embraces sister chromatids through interphase to promote their pairing. In preparation for mitosis, most cohesin is stripped from the chromosome arms in prophase by a poorly defined process that is associated with cohesin phosphorylation. In the fission yeast Schizosaccharomyces pombe this prophase pathway is dependent on the cohesin-related Smc5/6 complex, and this requirement is heightened in Smc5/6 hypomorphs by DNA damage, replication stress and Topoisomerase II (Top2) dysfunction...
April 5, 2017: Current Genetics
https://www.readbyqxmd.com/read/28369554/the-haploinsufficient-tumor-suppressor-cux1-acts-as-an-analog-transcriptional-regulator-that-controls-target-genes-through-distal-enhancers-that-loop-to-target-promoters
#12
Robert K Arthur, Ningfei An, Saira Khan, Megan E McNerney
One third of tumor suppressors are haploinsufficient transcriptional regulators, yet it remains unknown how a 50% reduction of a transcription factor is translated at the cis-regulatory level into a malignant transcriptional program. We studied CUX1, a haploinsufficient transcription factor that is recurrently mutated in hematopoietic and solid tumors. We determined CUX1 DNA-binding and target gene regulation in the wildtype and haploinsufficient states. CUX1 binds with transcriptional activators and cohesin at distal enhancers across three different human cell types...
March 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28368372/ercc1-xpf-cooperates-with-ctcf-and-cohesin-to%C3%A2-facilitate-the-developmental-silencing-of-imprinted%C3%A2-genes
#13
Georgia Chatzinikolaou, Zivkos Apostolou, Tamara Aid-Pavlidis, Anna Ioannidou, Ismene Karakasilioti, Giorgio L Papadopoulos, Michalis Aivaliotis, Maria Tsekrekou, John Strouboulis, Theodore Kosteas, George A Garinis
Inborn defects in DNA repair are associated with complex developmental disorders whose causal mechanisms are poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development...
April 3, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28364521/rna-immunoprecipitation-identifies-novel-targets-of-dazl-in-human-foetal-ovary
#14
Roseanne Rosario, Richard W P Smith, Ian R Adams, Richard A Anderson
Study question: Can novel meiotic RNA targets of DAZL (deleted in azoospermia-like) be identified in the human foetal ovary? Summary answer: SYCP1 (synaptonemal complex protein-1), TEX11 (testis expressed 11) and SMC1B (structural maintenance of chromosomes 1B) are novel DAZL targets in the human foetal ovary, thus DAZL may have previously unrecognised roles in the translational regulation of RNAs involved in chromosome cohesion and DNA recombination in the oocyte from the time of initiation of meiosis...
March 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28352327/downregulated-stromal-antigen-2-expression-in-de-novo-acute-myeloid-leukemia-patients
#15
Qiaoyan Han, Xuefeng He, Lili Wu, Feng Gao, Jinsong Ye, Lingyu Wu, Lu Chen, Xin Jiang, Miao Sun, Suning Chen
The stromal antigen 2 (STAG2) gene encodes a component of the cohesin complex that participates in the regulation of sister chromatid separation during mitosis. When activated, STAG2 may act as a 'caretaker' tumor suppressor gene. As it is unknown whether STAG2 gene is responsible for the occurrence and associated with the prognosis of acute myeloid leukemia (AML), the present study analyzed the relative expression levels of STAG2 in 127 de novo AML patients and 17 healthy volunteers using reverse transcription-quantitative polymerase chain reaction...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28343969/pds5-regulates-sister-chromatid-cohesion-and-chromosome-bi-orientation-through-a-conserved-protein-interaction-module
#16
Yuhei Goto, Yuya Yamagishi, Miyuki Shintomi-Kawamura, Mayumi Abe, Yuji Tanno, Yoshinori Watanabe
Sister-chromatid cohesion is established by the cohesin complex in S phase and persists until metaphase, when sister chromatids are captured by microtubules emanating from opposite poles [1]. The Aurora-B-containing chromosome passenger complex (CPC) plays a crucial role in achieving chromosome bi-orientation by correcting erroneous microtubule attachment [2]. The centromeric localization of the CPC relies largely on histone H3-T3 phosphorylation (H3-pT3), which is mediated by the mitotic histone kinase Haspin/Hrk1 [3-5]...
April 3, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28343965/the-n-terminal-non-kinase-domain-mediated-binding-of-haspin-to-pds5b-protects-centromeric-cohesion-in-mitosis
#17
Linli Zhou, Cai Liang, Qinfu Chen, Zhenlei Zhang, Bo Zhang, Haiyan Yan, Feifei Qi, Miao Zhang, Qi Yi, Youchen Guan, Xingfeng Xiang, Xiaoqing Zhang, Sheng Ye, Fangwei Wang
Sister-chromatid cohesion, mediated by the multi-subunit cohesin complex, must be precisely regulated to prevent chromosome mis-segregation. In prophase and prometaphase, whereas the bulk of cohesin on chromosome arms is removed by its antagonist Wapl, cohesin at centromeres is retained to ensure chromosome biorientation until anaphase onset. It remains incompletely understood how centromeric cohesin is protected against Wapl in mitosis. Here we show that the mitotic histone kinase Haspin binds to the cohesin regulatory subunit Pds5B through a conserved YGA/R motif in its non-catalytic N terminus, which is similar to the recently reported YSR-motif-dependent binding of Wapl to Pds5B...
April 3, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28335590/roles-of-budding-yeast-hrr25-in-recombination-and-sporulation
#18
Min-Su Lee, Jeong Hwan Joo, Keunpil Kim
Hrr25, a casein kinase 1 δ/ε homolog in budding yeast, is essential to set up mono-orientation of sister kinetochores during meiosis. Hrr25 kinase activity coordinates sister chromatid cohesion via cohesin phosphorylation. Here, we investigated the prophase roles of Hrr25 using the auxin-inducible degron system and by ectopic expression of Hrr25 during yeast meiosis. Hrr25 mediates nuclear division in meiosis I but does not affect DNA replication. We also found that initiation of meiotic double-strand breaks as well as joint molecule formation were normal in HRR25-deficient cells...
March 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28314726/global-distribution-patterns-and-pangenomic-diversity-of-the-candidate-phylum-latescibacteria-ws3
#19
Ibrahim F Farag, Noha H Youssef, Mostafa S Elshahed
We investigated the global distribution patterns and pangenomic diversity of the candidate phylum "Latescibacteria" (WS3) in 16S rRNA gene as well as metagenomic datasets. We document distinct distribution patterns for various "Latescibacteria" orders in 16S rRNA gene datasets, with prevalence of orders sediment_1 in terrestrial, PBSIII_9 in groundwater and temperate freshwater, and GN03 in pelagic marine, saline-hypersaline, and wastewater habitats. Using a fragment recruitment approach, we identified 68.9 Mb of "Latescibacteria"-affiliated contigs in publicly available metagenomic datasets comprising 73,079 proteins...
March 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28314340/cohesin-and-condensin-methods-and-protocols
#20
(no author information available yet)
No abstract text is available yet for this article.
March 2017: Anticancer Research
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