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DEAD helicase

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https://www.readbyqxmd.com/read/29037760/biochemical-differences-and-similarities-between-the-dead-box-helicase-orthologs-ddx3x-and-ded1p
#1
Deepak Sharma, Andrea A Putnam, Eckhard Jankowsky
DDX3X is a conserved DEAD-box RNA helicase involved in translation initiation and other processes of RNA metabolism. Mutations in human DDX3X and deregulation of its expression are linked to tumorigenesis and intellectual disability. The protein is also targeted by diverse viruses. Previous studies demonstrated helicase and NTPase activities for DDX3X, but important biochemical features of the enzyme remain unclear. Here, we systematically characterize enzymatic activities of human DDX3X and compare these to its closely related S...
October 13, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28965870/targeting-rna-helicases-in-cancer-the-translation-trap
#2
REVIEW
Marise R Heerma van Voss, Paul J van Diest, Venu Raman
Cancer cells are reliant on the cellular translational machinery for both global elevation of protein synthesis and the translation of specific mRNAs that promote tumor cell survival. Targeting translational control in cancer is therefore increasingly recognized as a promising therapeutic strategy. In this regard, DEAD/H box RNA helicases are a very interesting group of proteins, with several family members regulating mRNA translation in cancer cells. In this review, we delineate the mechanisms by which DEAD/H box proteins modulate oncogenic translation and how inhibition of these RNA helicases can be exploited for anti-cancer therapeutics...
September 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28964860/fish-ddx3x-exerts-antiviral-function-against-grouper-nervous-necrosis-virus-infection
#3
Jiaxin Liu, Xiaohong Huang, Yepin Yu, Jingcheng Zhang, Songwei Ni, Yin Hu, Youhua Huang, Qiwei Qin
Human DEAD box ATP-dependent RNA helicase DDX3X has been demonstrated to exert crucial functions in carcinogenesis and antiviral immune response. However, to our knowledge, few information focused on the functions of fish DDX3X. In this study, we cloned and characterized a DDX3X homolog from orange spotted grouper (Epinephelus coioides) (EcDDX3X). EcDDX3X encoded a 733-amino acid protein which shared 97% and 76% identity to spiny damselfish (Acanthochromis polyacanthus) and human (Homo sapiens), respectively...
September 28, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28924058/localization-of-cdc7-protein-kinase-during-dna-replication-in-saccharomyces-cerevisiae
#4
Daniel Rossbach, D Suzi Bryan, Jay R Hesselberth, Robert Sclafani
DDK, a conserved serine-threonine protein kinase composed of a regulatory subunit, Dbf4, and a catalytic subunit, Cdc7, is essential for DNA replication initiation during S phase of the cell cycle through MCM2-7 helicase phosphorylation. The biological significance of DDK is well characterized, but the full mechanism of how DDK associates with substrates remains unclear. Cdc7 is bound to chromatin in the Saccharomyces cerevisiae genome throughout the cell cycle, but there is little empirical evidence as to specific Cdc7 binding locations...
September 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28912341/the-role-of-blm-helicase-in-homologous-recombination-gene-conversion-tract-length-and-recombination-between-diverged-sequences-in-drosophila
#5
Henry A Ertl, Daniel P Russo, Noori Srivastava, Joseph T Brooks, Thu N Dao, Jeannine R LaRocque
DNA double-strand breaks (DSBs) are a particularly deleterious class of DNA damage that threatens genome integrity. DSBs are repaired by three pathways: non-homologous end joining (NHEJ), homologous recombination (HR), and single-strand annealing (SSA). Drosophila melanogaster Blm (DmBlm) is the ortholog of Saccharomyces cerevisiae SGS1 and human BLM, and has been shown to suppress crossovers in mitotic cells and repair mitotic DNA gaps via HR. To further elucidate the role of DmBlm in repair of a simple DSB, and in particular recombination mechanisms, we utilized the DR-white and DR-white...
September 14, 2017: Genetics
https://www.readbyqxmd.com/read/28869602/targeting-mitochondrial-translation-by-inhibiting-ddx3-a-novel-radiosensitization-strategy-for-cancer-treatment
#6
M R Heerma van Voss, F Vesuna, G M Bol, J Afzal, S Tantravedi, Y Bergman, K Kammers, M Lehar, R Malek, M Ballew, N Ter Hoeve, D Abou, D Thorek, C Berlinicke, M Yazdankhah, D Sinha, A Le, R Abrahams, P T Tran, P J van Diest, V Raman
DDX3 is a DEAD box RNA helicase with oncogenic properties. RK-33 is developed as a small-molecule inhibitor of DDX3 and showed potent radiosensitizing activity in preclinical tumor models. This study aimed to assess DDX3 as a target in breast cancer and to elucidate how RK-33 exerts its anti-neoplastic effects. High DDX3 expression was present in 35% of breast cancer patient samples and correlated with markers of aggressiveness and shorter survival. With a quantitative proteomics approach, we identified proteins involved in the mitochondrial translation and respiratory electron transport pathways to be significantly downregulated after RK-33 or DDX3 knockdown...
September 4, 2017: Oncogene
https://www.readbyqxmd.com/read/28854738/cgii-cleaves-dna-using-a-mechanism-distinct-from-other-atp-dependent-restriction-endonucleases
#7
Paulius Toliusis, Mindaugas Zaremba, Arunas Silanskas, Mark D Szczelkun, Virginijus Siksnys
The restriction endonuclease CglI from Corynebacterium glutamicum recognizes an asymmetric 5'-GCCGC-3' site and cleaves the DNA 7 and 6/7 nucleotides downstream on the top and bottom DNA strands, respectively, in an NTP-hydrolysis dependent reaction. CglI is composed of two different proteins: an endonuclease (R.CglI) and a DEAD-family helicase-like ATPase (H.CglI). These subunits form a heterotetrameric complex with R2H2 stoichiometry. However, the R2H2·CglI complex has only one nuclease active site sufficient to cut one DNA strand suggesting that two complexes are required to introduce a double strand break...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28846086/the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#8
Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao
DEAD-box (DDX) helicases are vital for the recognition of RNA and metabolism and are critical for the initiation of antiviral innate immunity. Modification of RNA is involved in many biological processes; however, its role in antiviral innate immunity has remained unclear. Here we found that nuclear DDX member DDX46 inhibited the production of type I interferons after viral infection. DDX46 bound Mavs, Traf3 and Traf6 transcripts (which encode signaling molecules involved in antiviral responses) via their conserved CCGGUU element...
October 2017: Nature Immunology
https://www.readbyqxmd.com/read/28842848/dead-box-helicase-6-ddx6-is-a-new-negative-regulator-for-milk-synthesis-and-proliferation-of-bovine-mammary-epithelial-cells
#9
Zhen Zhen, Minghui Zhang, Xiaohan Yuan, Bo Qu, Yanbo Yu, Xuejun Gao, Youwen Qiu
Milk synthesis of bovine mammary gland is a complex biological process that is regulated by hormones and nutrients, but the mechanism of these regulations still needs further research. DEAD-box helicase 6 (DDX6) is an important member of the RNA helicase family, involved in the regulation of mRNA storage and translation in different systems, but its physiological role and mechanism are largely unclear. In this study, we describe DDX6 as a potentially novel negative regulator for milk synthesis and proliferation of bovine mammary epithelial cells (BMECs)...
August 25, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28842590/ddx3-localizes-to-the-centrosome-and-prevents-multipolar-mitosis-by-epigenetically-and-translationally-modulating-p53-expression
#10
Wei-Ju Chen, Wei-Ting Wang, Tsung-Yuan Tsai, Hao-Kang Li, Yan-Hwa Wu Lee
The DEAD-box RNA helicase DDX3 plays divergent roles in tumorigenesis, however, its function in mitosis is unclear. Immunofluorescence indicated that DDX3 localized to centrosome throughout the cell cycle and colocalized with centrosome-associated p53 during mitosis in HCT116 and U2OS cells. DDX3 depletion promoted chromosome misalignment, segregation defects and multipolar mitosis, eventually leading to G2/M delay and cell death. DDX3 prevented multipolar mitosis by inactivation and coalescence of supernumerary centrosomes...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819113/insights-into-the-role-of-endonuclease-v-in-rna-metabolism-in-trypanosoma-brucei
#11
Daniel García-Caballero, Guiomar Pérez-Moreno, Antonio M Estévez, Luis Miguel Ruíz-Pérez, Antonio E Vidal, Dolores González-Pacanowska
Inosine may arise in DNA as a result of oxidative deamination of adenine or misincorporation of deoxyinosine triphosphate during replication. On the other hand, the occurrence of inosine in RNA is considered a normal and essential modification induced by specific adenosine deaminases acting on mRNA and tRNA. In prokaryotes, endonuclease V (EndoV) can recognize and cleave inosine-containing DNA. In contrast, mammalian EndoVs preferentially cleave inosine-containing RNA, suggesting a role in RNA metabolism for the eukaryotic members of this protein family...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807014/epigenetic-reprogramming-converts-human-wharton-s-jelly-mesenchymal-stem-cells-into-functional-cardiomyocytes-by-differential-regulation-of-wnt-mediators
#12
G Bhuvanalakshmi, Frank Arfuso, Alan Prem Kumar, Arun Dharmarajan, Sudha Warrier
BACKGROUND: Lineage commitment of mesenchymal stem cells (MSCs) to cardiac differentiation is controlled by transcription factors that are regulated by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Here, we studied the differentiation of human Wharton's jelly MSCs (WJMSCs) into the cardiomyocyte lineage via epigenetic manipulations. METHODS: We introduced these changes using inhibitors of DNA methyl transferase and histone deacetylase, DC301, DC302, and DC303, in various combinations...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28790157/sirt7-and-the-dead-box-helicase-ddx21-cooperate-to-resolve-genomic-r-loops-and-safeguard-genome-stability
#13
Chenlin Song, Agnes Hotz-Wagenblatt, Renate Voit, Ingrid Grummt
R loops are three-stranded nucleic acid structures consisting of an RNA:DNA heteroduplex and a "looped-out" nontemplate strand. As aberrant formation and persistence of R loops block transcription elongation and cause DNA damage, mechanisms that resolve R loops are essential for genome stability. Here we show that the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase DDX21 efficiently unwinds R loops and that depletion of DDX21 leads to accumulation of cellular R loops and DNA damage. Significantly, the activity of DDX21 is regulated by acetylation...
August 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28761359/nuclear-ddx3-expression-predicts-poor-outcome-in-colorectal-and-breast-cancer
#14
Marise R Heerma van Voss, Farhad Vesuna, Guus M Bol, Jan Meeldijk, Ana Raman, G Johan Offerhaus, Horst Buerger, Arvind H Patel, Elsken van der Wall, Paul J van Diest, Venu Raman
PURPOSE: DEAD box protein 3 (DDX3) is an RNA helicase with oncogenic properties that shuttles between the cytoplasm and nucleus. The majority of DDX3 is found in the cytoplasm, but a subset of tumors has distinct nuclear DDX3 localization of yet unknown biological significance. This study aimed to evaluate the significance of and mechanisms behind nuclear DDX3 expression in colorectal and breast cancer. METHODS: Expression of nuclear DDX3 and the nuclear exporter chromosome region maintenance 1 (CRM1) was evaluated by immunohistochemistry in 304 colorectal and 292 breast cancer patient samples...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28757063/atp-competitive-marine-derived-natural-products-that-target-the-dead-box-helicase-eif4a
#15
Joseph Tillotson, Magdalena Kedzior, Larissa Guimarães, Alison B Ross, Tara L Peters, Andrew J Ambrose, Cody J Schmidlin, Donna D Zhang, Letícia V Costa-Lotufo, Abimael D Rodríguez, Jonathan H Schatz, Eli Chapman
Activation of translation initiation is a common trait of cancer cells. Formation of the heterotrimeric eukaryotic initiation factor F (eIF4F) complex is the rate-limiting step in 5' m7GpppN cap-dependent translation. This trimeric complex includes the eIF4E cap binding protein, the eIF4G scaffolding protein, and the DEAD box RNA helicase eIF4A. eIF4A is an ATP-dependent helicase and because it is the only enzyme in the eIF4F complex, it has been shown to be a potential therapeutic target for a variety of malignancies...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28746868/ddx6-represses-aberrant-activation-of-interferon-stimulated-genes
#16
Jennifer H Lumb, Qin Li, Lauren M Popov, Siyuan Ding, Marie T Keith, Bryan D Merrill, Harry B Greenberg, Jin Billy Li, Jan E Carette
The innate immune system tightly regulates activation of interferon-stimulated genes (ISGs) to avoid inappropriate expression. Pathological ISG activation resulting from aberrant nucleic acid metabolism has been implicated in autoimmune disease; however, the mechanisms governing ISG suppression are unknown. Through a genome-wide genetic screen, we identified DEAD-box helicase 6 (DDX6) as a suppressor of ISGs. Genetic ablation of DDX6 induced global upregulation of ISGs and other immune genes. ISG upregulation proved cell intrinsic, imposing an antiviral state and making cells refractory to divergent families of RNA viruses...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28712727/error-prone-splicing-controlled-by-the-ubiquitin-relative-hub1
#17
Ramazan Karaduman, Sittinan Chanarat, Boris Pfander, Stefan Jentsch
Accurate pre-mRNA splicing is needed for correct gene expression and relies on faithful splice site recognition. Here, we show that the ubiquitin-like protein Hub1 binds to the DEAD-box helicase Prp5, a key regulator of early spliceosome assembly, and stimulates its ATPase activity thereby enhancing splicing and relaxing fidelity. High Hub1 levels enhance splicing efficiency but also cause missplicing by tolerating suboptimal splice sites and branchpoint sequences. Notably, Prp5 itself is regulated by a Hub1-dependent negative feedback loop...
August 3, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28711741/confirmation-that-mutations-in-ddx59-cause-an-autosomal-recessive-form-of-oral-facial-digital-syndrome-further-delineation-of-the-ddx59-phenotype-in-two-new-families
#18
Sara Faily, Rahat Perveen, Jill Urquhart, Kate Chandler, Jill Clayton-Smith
We report three probands from two unrelated consanguineous families of South Asian origin who all carry the same rare novel homozygous variant within the dead box helicase gene DDX59 in association with features of oral-facial-digital syndrome (OFDS). DDX59 variants have been reported previously in an unclassified, autosomal recessive form of OFDS; clinically associated with features including tongue lobulation, cleft palate, frontal bossing, hypertelorism and postaxial polydactyly. All three probands had lobulated tongues with tongue hamartomas, abnormal tongue tip, developmental delay and microcephaly, with just one proband demonstrating polydactlyly...
October 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28705764/a-survey-of-ddx21-activity-during-rev-rre-complex-formation
#19
John A Hammond, Li Zhou, Rajan Lamichhane, Hui-Yi Chu, David P Millar, Larry Gerace, James R Williamson
HIV-1 requires a specialized nuclear export pathway to transport unspliced and partially spliced viral transcripts to the cytoplasm. Central to this pathway is the viral protein Rev, which binds to the Rev response element in stem IIB located on unspliced viral transcripts and subsequently oligomerizes in a cooperative manner. Previous work identified a number of cellular DEAD-box helicases as in vivo binding partners of Rev, and siRNA experiments indicated a functional role for many in the HIV replication cycle...
July 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28697848/roles-of-rnase-p-and-its-subunits
#20
REVIEW
Nayef Jarrous
Recent studies show that nuclear RNase P is linked to chromatin structure and function. Thus, variants of this ribonucleoprotein (RNP) complex bind to chromatin of small noncoding RNA genes; integrate into initiation complexes of RNA polymerase (Pol) III; repress histone H3.3 nucleosome deposition; control tRNA and PIWI-interacting RNA (piRNA) gene clusters for genome defense; and respond to Werner syndrome helicase (WRN)-related replication stress and DNA double-strand breaks (DSBs). Likewise, the related RNase MRP and RMRP-TERT (telomerase reverse transcriptase) are implicated in RNA-dependent RNA polymerization for chromatin silencing, whereas the telomerase carries out RNA-dependent DNA polymerization for telomere lengthening...
July 8, 2017: Trends in Genetics: TIG
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