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https://www.readbyqxmd.com/read/28604691/ino80-exchanges-h2a-z-for-h2a-by-translocating-on-dna-proximal-to-histone-dimers
#1
Sandipan Brahma, Maheshi I Udugama, Jongseong Kim, Arjan Hada, Saurabh K Bhardwaj, Solomon G Hailu, Tae-Hee Lee, Blaine Bartholomew
ATP-dependent chromatin remodellers modulate nucleosome dynamics by mobilizing or disassembling nucleosomes, as well as altering nucleosome composition. These chromatin remodellers generally function by translocating along nucleosomal DNA at the H3-H4 interface of nucleosomes. Here we show that, unlike other remodellers, INO80 translocates along DNA at the H2A-H2B interface of nucleosomes and persistently displaces DNA from the surface of H2A-H2B. DNA translocation and DNA torsional strain created near the entry site of nucleosomes by INO80 promotes both the mobilization of nucleosomes and the selective exchange of H2A...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28591576/regulation-of-rvb1-rvb2-by-a-domain-within-the-ino80-chromatin-remodeling-complex-implicates-the-yeast-rvbs-as-protein-assembly-chaperones
#2
Coral Y Zhou, Caitlin I Stoddard, Jonathan B Johnston, Michael J Trnka, Ignacia Echeverria, Eugene Palovcak, Andrej Sali, Alma L Burlingame, Yifan Cheng, Geeta J Narlikar
The hexameric AAA+ ATPases Rvb1 and Rvb2 (Rvbs) are essential for diverse processes ranging from metabolic signaling to chromatin remodeling, but their functions are unknown. While originally thought to act as helicases, recent proposals suggest that Rvbs act as protein assembly chaperones. However, experimental evidence for chaperone-like behavior is lacking. Here, we identify a potent protein activator of the Rvbs, a domain in the Ino80 ATPase subunit of the INO80 chromatin-remodeling complex, termed Ino80INS...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28585918/crosstalk-within-a-functional-ino80-complex-dimer-regulates-nucleosome-sliding
#3
Oliver Willhoft, Elizabeth A McCormack, Ricardo J Aramayo, Rohan Bythell-Douglas, Lorraine Ocloo, Xiaodong Zhang, Dale B Wigley
Several chromatin remodellers have the ability to space nucleosomes on DNA. For ISWI remodellers, this involves an interplay between H4 histone tails, the AutoN and NegC motifs of the motor domains that together regulate ATPase activity and sense the length of DNA flanking the nucleosome. By contrast, the INO80 complex also spaces nucleosomes but is not regulated by H4 tails and lacks the AutoN and NegC motifs. Instead nucleosome sliding requires cooperativity between two INO80 complexes that monitor DNA length simultaneously on either side of the nucleosome during sliding...
June 6, 2017: ELife
https://www.readbyqxmd.com/read/28514650/the-ino80-complex-removes-h2a-z-to-promote-presynaptic-filament-formation-during-homologous-recombination
#4
Claudio A Lademann, Jörg Renkawitz, Boris Pfander, Stefan Jentsch
The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR-DNA end resection and presynaptic filament formation...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28403234/transcriptional-repression-of-frequency-by-the-iec-1-ino80-complex-is-required-for-normal-neurospora-circadian-clock-function
#5
Kexin Gai, Xuemei Cao, Qing Dong, Zhaolan Ding, Yashang Wei, Yingchun Liu, Xiao Liu, Qun He
Rhythmic activation and repression of the frequency (frq) gene are essential for normal function of the Neurospora circadian clock. WHITE COLLAR (WC) complex, the positive element of the Neurospora circadian system, is responsible for stimulation of frq transcription. We report that a C2H2 finger domain-containing protein IEC-1 and its associated chromatin remodeling complex INO80 play important roles in normal Neurospora circadian clock function. In iec-1KO strains, circadian rhythms are abolished, and the frq transcript levels are increased compared to that of the wild-type strain...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28402505/dicer-and-zrf1-contribute-to-chromatin-decondensation-during-nucleotide-excision-repair
#6
Shalaka Chitale, Holger Richly
Repair of damaged DNA relies on the recruitment of DNA repair factors in a well orchestrated manner. As a prerequisite, the chromatin needs to be decondensed by chromatin remodelers to allow for binding of repair factors and for DNA repair to occur. Recent studies have implicated members of the SWI/SNF and INO80 families as well as PARP1 in nucleotide excision repair (NER). In this study, we report that the endonuclease DICER is implicated in chromatin decondensation during NER. In response to UV irradiation, DICER is recruited to chromatin in a ZRF1-mediated manner...
June 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28338506/a-preliminary-report-radical-surgery-and-stem-cell-transplantation-for-the-treatment-of-patients-with-pancreatic-cancer
#7
Brigitta Omazic, Burcu Ayoglu, Matthias Löhr, Ralf Segersvärd, Caroline Verbeke, Isabelle Magalhaes, Zuzana Potacova, Jonas Mattsson, Alexei Terman, Sam Ghazi, Nils Albiin, Nikolaos Kartalis, Peter Nilsson, Thomas Poiret, Liu Zhenjiang, Rainer Heuchel, Jochen M Schwenk, Johan Permert, Markus J Maeurer, Olle Ringden
We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT...
March 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28272416/identification-of-topological-network-modules-in-perturbed-protein-interaction-networks
#8
Mihaela E Sardiu, Joshua M Gilmore, Brad Groppe, Laurence Florens, Michael P Washburn
Biological networks consist of functional modules, however detecting and characterizing such modules in networks remains challenging. Perturbing networks is one strategy for identifying modules. Here we used an advanced mathematical approach named topological data analysis (TDA) to interrogate two perturbed networks. In one, we disrupted the S. cerevisiae INO80 protein interaction network by isolating complexes after protein complex components were deleted from the genome. In the second, we reanalyzed previously published data demonstrating the disruption of the human Sin3 network with a histone deacetylase inhibitor...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270832/actin-family-proteins-in-the-human-ino80-chromatin-remodeling-complex-exhibit-functional-roles-in-the-induction-of-heme-oxygenase-1-with-hemin
#9
Yuichiro Takahashi, Hirokazu Murakami, Yusuke Akiyama, Yasutake Katoh, Yukako Oma, Hitoshi Nishijima, Kei-Ichi Shibahara, Kazuhiko Igarashi, Masahiko Harata
Nuclear actin family proteins, comprising of actin and actin-related proteins (Arps), are essential functional components of the multiple chromatin remodeling complexes. The INO80 chromatin remodeling complex, which is evolutionarily conserved and has roles in transcription, DNA replication and repair, consists of actin and actin-related proteins Arp4, Arp5, and Arp8. We generated Arp5 knockout (KO) and Arp8 KO cells from the human Nalm-6 pre-B cell line and used these KO cells to examine the roles of Arp5 and Arp8 in the transcriptional regulation mediated by the INO80 complex...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28254775/global-analysis-of-sumo-binding-proteins-identifies-sumoylation-as-a-key-regulator-of-the-ino80-chromatin-remodeling-complex
#10
Eric Cox, Woochang Hwang, Ijeoma Uzoma, Jianfei Hu, Catherine M Guzzo, Junseop Jeong, Michael J Matunis, Jiang Qian, Heng Zhu, Seth Blackshaw
SUMOylation is a critical regulator of a broad range of cellular processes, and is thought to do so in part by modulation of protein interaction. To comprehensively identify human proteins whose interaction is modulated by SUMOylation, we developed an in vitro binding assay using human proteome microarrays to identify targets of SUMO1 and SUMO2. We then integrated these results with protein SUMOylation and protein-protein interaction data to perform network motif analysis. We focused on a single network motif we termed a SUMOmodPPI (SUMO-modulated Protein-Protein Interaction) that included the INO80 chromatin remodeling complex subunits TFPT and INO80E...
May 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28209126/a-meta-analysis-reveals-complex-regulatory-properties-at-taf14-repressed-genes
#11
Josipa Nemet, Nikolina Vidan, Mary Sopta
BACKGROUND: Regulation of gene transcription in response to stress is central to a cell's ability to cope with environmental challenges. Taf14 is a YEATS domain protein in S.cerevisiae that physically associates with several transcriptionally relevant multisubunit complexes including the general transcription factors TFIID and TFIIF and the chromatin-modifying complexes SWI/SNF, INO80, RSC and NuA3. TAF14 deletion strains are sensitive to a variety of stresses suggesting that it plays a role in the transcriptional stress response...
February 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28147275/visualization-of-chromatin-decompaction-and-break-site-extrusion-as-predicted-by-statistical-polymer-modeling-of-single-locus-trajectories
#12
Assaf Amitai, Andrew Seeber, Susan M Gasser, David Holcman
Chromatin moves with subdiffusive and spatially constrained dynamics within the cell nucleus. Here, we use single-locus tracking by time-lapse fluorescence microscopy to uncover information regarding the forces that influence chromatin movement following the induction of a persistent DNA double-strand break (DSB). Using improved time-lapse imaging regimens, we monitor trajectories of tagged DNA loci at a high temporal resolution, which allows us to extract biophysical parameters through robust statistical analysis...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28122867/the-genetic-basis-of-hepatosplenic-t-cell-lymphoma
#13
Matthew McKinney, Andrea B Moffitt, Philippe Gaulard, Marion Travert, Laurence De Leval, Alina Nicolae, Mark Raffeld, Elaine S Jaffe, Stefania Pittaluga, Liqiang Xi, Tayla Heavican, Javeed Iqbal, Karim Belhadj, Marie Helene Delfau-Larue, Virginie Fataccioli, Magdalena B Czader, Izidore S Lossos, Jennifer R Chapman-Fredricks, Kristy L Richards, Yuri Fedoriw, Sarah L Ondrejka, Eric D Hsi, Lawrence Low, Dennis Weisenburger, Wing C Chan, Neha Mehta-Shah, Steven Horwitz, Leon Bernal-Mizrachi, Christopher R Flowers, Anne W Beaven, Mayur Parihar, Lucile Baseggio, Marie Parrens, Anne Moreau, Pierre Sujobert, Monika Pilichowska, Andrew M Evens, Amy Chadburn, Rex K H Au-Yeung, Gopesh Srivastava, William W L Choi, John R Goodlad, Igor Aurer, Sandra Basic-Kinda, Randy D Gascoyne, Nicholas S Davis, Guojie Li, Jenny Zhang, Deepthi Rajagopalan, Anupama Reddy, Cassandra Love, Shawn Levy, Yuan Zhuang, Jyotishka Datta, David B Dunson, Sandeep S Davé
Hepatosplenic T-cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole-exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy-number alterations in the disease. Chromatin-modifying genes, including SETD2, INO80, and ARID1B, were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%), for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS, and TP53SETD2 was the most frequently silenced gene in HSTL...
April 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28097693/distinguishing-between-biochemical-and-cellular-function-are-there-peptide-signatures-for-cellular-function-of-proteins
#14
Shruti Jain, Kausik Bhattacharyya, Rachit Bakshi, Ankita Narang, Vani Brahmachari
The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function...
January 18, 2017: Proteins
https://www.readbyqxmd.com/read/28067915/histone-degradation-in-response-to-dna-damage-enhances-chromatin-dynamics-and-recombination-rates
#15
Michael H Hauer, Andrew Seeber, Vijender Singh, Raphael Thierry, Ragna Sack, Assaf Amitai, Mariya Kryzhanovska, Jan Eglinger, David Holcman, Tom Owen-Hughes, Susan M Gasser
Nucleosomes are essential for proper chromatin organization and the maintenance of genome integrity. Histones are post-translationally modified and often evicted at sites of DNA breaks, facilitating the recruitment of repair factors. Whether such chromatin changes are localized or genome-wide is debated. Here we show that cellular levels of histones drop 20-40% in response to DNA damage. This histone loss occurs from chromatin, is proteasome-mediated and requires both the DNA damage checkpoint and the INO80 nucleosome remodeler...
February 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28064308/-structural-studies-of-chromatin-remodeling-factors
#16
REVIEW
O I Volokh, N I Derkacheva, V M Studitsky, O S Sokolova
Changes of chromatin structure require participation of chromatin remodeling factors (CRFs), which are ATP-dependent multisubunit complexes that change the structure of the nucleosome without covalently modifying its components. CRFs act together with other protein factors to regulate the extent of chromatin condensation. Four CRF families are currently distinguished based on their structural and biochemical characteristics: SWI/SNF, ISWI, Mi-2/CHD, and SWR/INO80. X-ray diffraction analysis and electron microscopy are the main methods to obtain structural information about macromolecules...
November 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28025392/ino80-represses-osmostress-induced-gene-expression-by-resetting-promoter-proximal-nucleosomes
#17
Eva Klopf, Heiko A Schmidt, Sandra Clauder-Münster, Lars M Steinmetz, Christoph Schüller
The conserved INO80 chromatin remodeling complex is involved in regulation of DNA damage repair, replication and transcription. It is commonly recruited to the transcription start region and contributes to the establishment of promoter-proximal nucleosomes. We find a substantial influence of INO80 on nucleosome dynamics and gene expression during stress induced transcription. Transcription induced by osmotic stress leads to genome-wide remodeling of promoter proximal nucleosomes. INO80 function is required for timely return of evicted nucleosomes to the 5΄ end of induced genes...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27989438/chromatin-controls-dna-replication-origin-selection-lagging-strand-synthesis-and-replication-fork-rates
#18
Christoph F Kurat, Joseph T P Yeeles, Harshil Patel, Anne Early, John F X Diffley
The integrity of eukaryotic genomes requires rapid and regulated chromatin replication. How this is accomplished is still poorly understood. Using purified yeast replication proteins and fully chromatinized templates, we have reconstituted this process in vitro. We show that chromatin enforces DNA replication origin specificity by preventing non-specific MCM helicase loading. Helicase activation occurs efficiently in the context of chromatin, but subsequent replisome progression requires the histone chaperone FACT (facilitates chromatin transcription)...
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/27939641/loss-of-function-mutations-in-yy1ap1-lead-to-grange-syndrome-and-a-fibromuscular-dysplasia-like-vascular-disease
#19
Dong-Chuan Guo, Xue-Yan Duan, Ellen S Regalado, Lauren Mellor-Crummey, Callie S Kwartler, Dong Kim, Kenneth Lieberman, Bert B A de Vries, Rolph Pfundt, Albert Schinzel, Dieter Kotzot, Xuetong Shen, Min-Lee Yang, Michael J Bamshad, Deborah A Nickerson, Heather L Gornik, Santhi K Ganesh, Alan C Braverman, Dorothy K Grange, Dianna M Milewicz
Fibromuscular dysplasia (FMD) is a heterogeneous group of non-atherosclerotic and non-inflammatory arterial diseases that primarily involves the renal and cerebrovascular arteries. Grange syndrome is an autosomal-recessive condition characterized by severe and early-onset vascular disease similar to FMD and variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities. Exome-sequencing analysis of DNA from three affected siblings with Grange syndrome identified compound heterozygous nonsense variants in YY1AP1, and homozygous nonsense or frameshift YY1AP1 variants were subsequently identified in additional unrelated probands with Grange syndrome...
January 5, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27919072/structure-and-regulation-of-the-chromatin-remodeller-iswi
#20
Lijuan Yan, Li Wang, Yuanyuan Tian, Xian Xia, Zhucheng Chen
ISWI is a member of the SWI2/SNF2 family of chromatin remodellers, which also includes Snf2, Chd1, and Ino80. ISWI is the catalytic subunit of several chromatin remodelling complexes, which mobilize nucleosomes along genomic DNA, promoting replication progression, transcription repression, heterochromatin formation, and many other nuclear processes. The ATPase motor of ISWI is an autonomous remodelling machine, whereas its carboxy (C)-terminal HAND-SAND-SLIDE (HSS) domain functions in binding extranucleosomal linker DNA...
December 15, 2016: Nature
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