Journal ArticleBiochim Biophys Acta Mol Basis Dis · January 2025
Virus-induced trabeculitis is considered a significant cause of uveitic glaucoma, being marked by a sudden increase in intraocular pressure and relatively mild inflammation in the anterior chamber of the eye. In previous proteome analyses of aqueous humor ...
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Journal ArticleElife · November 22, 2023
Visual signal transduction takes place within a stack of flattened membranous 'discs' enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large he ...
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Journal ArticleJ Extracell Biol · October 2023
The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age- ...
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Journal ArticlebioRxiv · August 29, 2023
Visual signal transduction takes place within a stack of flattened membranous "discs" enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large he ...
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Journal ArticleJ Proteome Res · August 4, 2023
Photoreceptor cells generate neuronal signals in response to capturing light. This process, called phototransduction, takes place in a highly specialized outer segment organelle. There are significant discrepancies in the reported amounts of many proteins ...
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Journal ArticleElife · July 14, 2023
The first steps of vision take place within a stack of tightly packed disc-shaped membranes, or 'discs', located in the outer segment compartment of photoreceptor cells. In rod photoreceptors, discs are enclosed inside the outer segment and contain deep in ...
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Journal ArticlebioRxiv · June 13, 2023
The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age- ...
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Journal ArticlebioRxiv · June 11, 2023
Photoreceptor cells generate neuronal signals in response to capturing light. This process, called phototransduction, takes place in a highly specialized outer segment organelle. There are significant discrepancies in the reported amounts of many proteins ...
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Journal ArticlebioRxiv · April 7, 2023
The first steps of vision take place within a stack of tightly packed disc-shaped membranes, or "discs", located in the outer segment compartment of photoreceptor cells. In rod photoreceptors, discs are enclosed inside the outer segment and contain deep in ...
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Journal ArticleProc Natl Acad Sci U S A · March 21, 2023
The photoreceptor outer segment is a modified cilium filled with hundreds of flattened "disc" membranes responsible for efficient light capture. To maintain photoreceptor health and functionality, outer segments are continuously renewed through the additio ...
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Journal ArticleElife · January 4, 2023
The small GTPase Arl3 is important for the enrichment of lipidated proteins to primary cilia, including the outer segment of photoreceptors. Human mutations in the small GTPase Arl3 cause both autosomal recessive and dominant inherited retinal dystrophies. ...
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Journal ArticleFront Ophthalmol (Lausanne) · 2023
INTRODUCTION: Extracellular matrix (ECM) materials accumulate in the trabecular meshwork (TM) tissue of patients with glaucoma, which is associated with a decrease in aqueous humor outflow and therefore an increase in intraocular pressure. To explore a pot ...
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Journal ArticleJ Clin Med · April 22, 2022
Herpetic anterior uveitis-associated ocular inflammation is commonly manifested with ocular hypertension and glaucoma. Relative to other viruses, cytomegalovirus (CMV) positive hypertensive anterior uveitis is associated with high recurrences of uveitis, a ...
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Journal ArticleJ Cell Mol Med · April 2022
Glaucoma, one of the leading causes of irreversible blindness, is commonly associated with elevated intraocular pressure due to impaired aqueous humour (AH) drainage through the trabecular meshwork. The aetiological mechanisms contributing to impaired AH o ...
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Journal ArticleFront Cell Dev Biol · 2022
Clinical use of glucocorticoids is associated with increased intraocular pressure (IOP), a major risk factor for glaucoma. Glucocorticoids have been reported to induce changes in actin cytoskeletal organization, cell adhesion, extracellular matrix, fibroge ...
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Journal ArticleBiochim Biophys Acta Mol Basis Dis · January 1, 2021
The molecular and cellular basis for cataract development in mice lacking dystrophin, a scaffolding protein that links the cytoskeleton to the extracellular matrix, is poorly understood. In this study, we characterized lenses derived from the dystrophin-de ...
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Journal ArticleMol Cell Proteomics · 2021
The outer segment (OS) organelle of vertebrate photoreceptors is a highly specialized cilium evolved to capture light and initiate light response. The plasma membrane which envelopes the OS plays vital and diverse roles in supporting photoreceptor function ...
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Journal ArticleJ Biol Chem · September 25, 2020
Strong evidence suggests that dysregulated lipid metabolism involving dysfunction of the retinal pigmented epithelium (RPE) underlies the pathogenesis of age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly. A ...
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Journal ArticleHum Mol Genet · July 29, 2020
Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of ...
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Journal ArticleNat Commun · July 3, 2020
Genes encoding cell-surface proteins control nervous system development and are implicated in neurological disorders. These genes produce alternative mRNA isoforms which remain poorly characterized, impeding understanding of how disease-associated mutation ...
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Journal ArticleProc Natl Acad Sci U S A · December 26, 2019
The light-sensitive outer segment of the vertebrate photoreceptor is a highly modified primary cilium filled with disc-shaped membranes that provide a vast surface for efficient photon capture. The formation of each disc is initiated by a ciliary membrane ...
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Journal ArticleAdv Exp Med Biol · 2019
The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier, provides nutrients, recycles visual pigment, and removes spent discs from the photoreceptors, among many other functions. Because of these critical roles in visual homeostasis, t ...
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Journal ArticleSci Rep · November 20, 2018
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...
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Journal ArticleNat Commun · April 30, 2018
Inherited retinal degenerations, affecting more than 2 million people worldwide, are caused by mutations in over 200 genes. This suggests that the most efficient therapeutic strategies would be mutation independent, i.e., targeting common pathological cond ...
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Journal ArticleInvest Ophthalmol Vis Sci · April 1, 2018
PURPOSE: Lysophosphatidic acid (LPA), a bioactive lipid, has been shown to increase resistance to aqueous humor outflow (AH) through the trabecular meshwork (TM). The molecular basis for this response of the TM to LPA, however, is not completely understood ...
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Journal ArticleeNeuro · 2018
The heterotrimeric G-protein transducin mediates visual signaling in vertebrate photoreceptor cells. Many aspects of the function of transducin were learned from knock-out mice lacking its individual subunits. Of particular interest is the knockout of its ...
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Journal ArticleJ Cell Physiol · September 2017
Glaucoma, a leading cause of irreversible blindness, is commonly associated with elevated intraocular pressure (IOP) due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM). Although dysregulated production and organization of extr ...
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Journal ArticleSci Rep · July 7, 2017
The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier in the eye and its polarity is responsible for directional secretion and uptake of proteins, lipoprotein particles and extracellular vesicles (EVs). Such a secretional division di ...
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Journal ArticleInvest Ophthalmol Vis Sci · June 1, 2017
PURPOSE: Complement activation is implicated in the pathogenesis of age-related macular degeneration (AMD). Apolipoprotein E (ApoE) and complement activation products such as membrane attack complex (MAC) are present in eyes of individuals with AMD. Herein ...
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Journal ArticleInvest Ophthalmol Vis Sci · December 1, 2016
PURPOSE: To determine the role and regulation of growth differentiation factor-15 (GDF-15), a TGF-β-related cytokine in human trabecular meshwork (TM) cells in the context of aqueous humor (AH) outflow and IOP. METHODS: Regulation of expression by external ...
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Journal ArticleBiochemistry · September 13, 2016
The light-sensing outer segments of photoreceptor cells harbor hundreds of flattened membranous discs containing the visual pigment, rhodopsin, and all the proteins necessary for visual signal transduction. PRCD (progressive rod-cone degeneration) protein ...
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Journal ArticleProcess Biochemistry · August 1, 2013
The bacterium Lysobacter species strain XL1 is known as a producer of extracellular lytic enzymes, which are capable of degrading cell wall components of other bacteria and simple eukaryotes. This ability determines the ecological, medical and agricultural ...
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Journal ArticleProc Natl Acad Sci U S A · June 11, 2013
Inherited retinal degenerations, caused by mutations in over 100 individual genes, affect approximately 2 million people worldwide. Many of the underlying mutations cause protein misfolding or mistargeting in affected photoreceptors. This places an increas ...
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Journal ArticleJ Proteome Res · June 7, 2013
Visual signal transduction takes place on the surface of flat membrane vesicles called photoreceptor discs, which reside inside the light-sensitive outer segment organelle of vertebrate photoreceptor cells. Although biochemical studies have indicated that ...
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Journal ArticleDev Biol · September 1, 2011
Transparency of the ocular lens depends on symmetric packing and membrane organization of highly elongated hexagonal fiber cells. These cells possess an extensive, well-ordered cortical cytoskeleton to maintain cell shape and to anchor membrane components. ...
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Journal ArticleMol Cell Proteomics · March 2011
The retina is a highly ordered tissue whose outermost layers are formed by subcellular compartments of photoreceptors generating light-evoked electrical responses. We studied protein distributions among individual photoreceptor compartments by separating t ...
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Journal ArticleInvest Ophthalmol Vis Sci · December 2010
PURPOSE: To understand the molecular basis for the known distinct contractile characteristics of trabecular meshwork (TM) and ciliary muscle (CM) cells, the cytoskeleton-enriched protein fractions of the TM and CM cells were isolated and characterized. MET ...
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Journal ArticleJ Neurosci · May 19, 2010
The remarkable ability of our vision to function under ever-changing conditions of ambient illumination is mediated by multiple molecular mechanisms regulating the light sensitivity of rods and cones. One such mechanism involves massive translocation of si ...
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Journal ArticleJ Biol Chem · February 12, 2010
The central enzyme of the visual transduction cascade, cGMP phosphodiesterase (PDE6), is regulated by its gamma-subunit (Pgamma), whose inhibitory constraint is released upon binding of activated transducin. It is generally believed that the last four or f ...
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Journal ArticleInvest Ophthalmol Vis Sci · April 2009
PURPOSE: Variations in the complement factor H (CFH) gene are tightly associated with age-related macular degeneration (AMD) across diverse populations. Of the many nonsynonymous coding variants in CFH, two are most strongly associated with increased risk ...
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Journal ArticleJ Cell Biol · November 3, 2008
Photoreceptors are compartmentalized neurons in which all proteins responsible for evoking visual signals are confined to the outer segment. Yet, the mechanisms responsible for establishing and maintaining photoreceptor compartmentalization are poorly unde ...
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Journal ArticleBiochem Biophys Res Commun · April 11, 2008
To understand lens fiber cell elongation- and differentiation-associated cytoskeletal remodeling, here we identified and characterized the major protein components of lens fiber cell Triton X-100 insoluble fraction by mass spectrometry and immunoblot analy ...
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Journal ArticleCell · December 28, 2007
The exosome complex plays a central and essential role in RNA metabolism. However, comprehensive studies of exosome substrates and functional analyses of its subunits are lacking. Here, we demonstrate that as opposed to yeast and metazoans the plant exosom ...
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Journal ArticleDifferentiation · October 2007
Myosin II, a molecular motor, plays a critical role in cell migration, cell shape changes, cell adhesion, and cytokinesis. To understand the role of myosin II in lens fiber cell elongation and differentiation, we determined the distribution pattern of nonm ...
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Journal ArticleJ Neurosci · January 31, 2007
Light causes massive translocation of G-protein transducin from the light-sensitive outer segment compartment of the rod photoreceptor cell. Remarkably, significant translocation is observed only when the light intensity exceeds a critical threshold level. ...
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Journal ArticleJ Biol Chem · February 18, 2005
The R7 subfamily of the regulators of G protein signaling (RGS) proteins is represented by four members broadly expressed in the mammalian nervous system. Here we report that in the brain all four R7 proteins form tight complexes with a previously unidenti ...
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Journal ArticleJ Biol Chem · April 25, 2003
G(s)alpha, G(i)alpha(1), and G(q)alpha subunits bind tubulin with high affinity, whereas transducin (G(t)alpha) does not. The interaction between tubulin and Galpha, which also involves the direct transfer of GTP from tubulin to Galpha (transactivation), i ...
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Journal ArticleJ Biol Chem · December 20, 2002
A yeast two-hybrid approach was used to discern possible new effectors for the betagamma subunit of heterotrimeric G proteins. Three of the clones isolated are structurally similar to Gbeta, each exhibiting the WD40 repeat motif. Two of these proteins, the ...
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Journal ArticleJ Biol Chem · October 5, 2001
RGS proteins regulate the duration of G protein signaling by increasing the rate of GTP hydrolysis on G protein alpha subunits. The complex of RGS9 with type 5 G protein beta subunit (G beta 5) is abundant in photoreceptors, where it stimulates the GTPase ...
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Journal ArticleJ Biol Chem · October 20, 2000
The photoreceptor-specific G protein transducin acts as a molecular switch, stimulating the activity of its downstream effector in its GTP-bound form and inactivating the effector upon GTP hydrolysis. This activity makes the rate of transducin GTPase an es ...
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Journal ArticleJ Biol Chem · September 29, 2000
Phosducin and phosducin-like protein regulate G protein signaling pathways by binding the betagamma subunit complex (Gbetagamma) and blocking Gbetagamma association with Galpha subunits, effector enzymes, or membranes. Both proteins are composed of two str ...
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Journal ArticleJ Biol Chem · March 26, 1999
RGS proteins (regulators of G protein signaling) are potent accelerators of the intrinsic GTPase activity of G protein alpha subunits (GAPs), thus controlling the response kinetics of a variety of cell signaling processes. Most RGS domains that have been s ...
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Journal ArticleJ Biol Chem · January 22, 1999
To understand the dynamics of conformational changes during G protein activation, surface exposed cysteine residues on Galpha were fluorescently labeled. Limited trypsinolysis and mutational analysis of recombinant Galphat/Galphai1 determined that two cyst ...
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OtherFASEB Journal · December 1, 1998
The molecular basis of selectivity in receptor-(î protein coupling has been explored by comparing the abilities of G protein heterotrimers containing chimeric Go subunits, comprised of various regions of Ga,i, Gat and Gft?. to function ally interact with d ...
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Journal ArticleScience · May 22, 1998
Both the alpha and betagamma subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins) communicate signals from receptors to effectors. Gbetagamma subunits can regulate a diverse array of effectors, including ion channels and enzymes. Gal ...
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Journal ArticleJ Biol Chem · December 19, 1997
The recognition between G protein and cognate receptor plays a key role in specific cellular responses to environmental stimuli. Here we explore specificity in receptor-G protein coupling by taking advantage of the ability of the 5-hydroxytryptamine1B (5-H ...
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ConferenceFASEB Journal · December 1, 1997
This work is a collaborative study by several laboratories directed at localizing sites of interaction between Gβγ, an important mediator of transmembrane signaling, and numerous downstream partners. To this end we have targeted residues on Gβγ that contac ...
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ConferenceFASEB Journal · December 1, 1997
Gβy-dependent interactions have profound effects on diverse signaling pathways. In many instances, Ga-GDP disrupts interactions between Gβy and its binding partners. The molecular basis of Gβy-dependent interactions with cellular proteins was studied by us ...
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ConferenceFASEB Journal · January 1, 1997
Helerotrimeric G proteins provide a signal transduction coupling between surface receptors and the effectors that regulate the concentration of the intraccllular second messengers. The specific recognition between G protein and cognate receptor plays a key ...
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Journal ArticleNature · January 25, 1996
The structure of a heterotrimeric G protein reveals the mechanism of the nucleotide-dependent engagement of the alpha and beta gamma subunits that regulates their interaction with receptor and effector molecules. The interaction involves two distinct inter ...
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Journal ArticleJ Biol Chem · January 5, 1996
The G protein transducin has been an often-used model for biochemical, structural, and mechanistic studies of G protein function. Experimental studies have been limited, however, by the inability to express quantities of mutants in heterologous systems wit ...
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Journal ArticleJ Biol Chem · June 2, 1995
The interaction between the GTP-bound form of the transducin alpha-subunit (G alpha t) and the gamma-subunit (P gamma) of cGMP phosphodiesterase (PDE) is a key event in effector activation during photon signal transduction. The carboxyl-terminal half of P ...
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Journal ArticleJ Biol Chem · August 5, 1994
The photoreceptor G-protein, transducin, belongs to the class of heterotrimeric GTP-binding proteins that transfer information from activated seven-span membrane receptors to effector enzymes or ion channels. Like other G-proteins, transducin acts as a mol ...
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Journal ArticleMethods · January 1, 1993
Cyclic GMP-phosphodiesterase (PDE) is the effector enzyme of vertebrate photoreceptor cells that regulates the level of the second messenger, cyclic GMP. PDE consists of catalytic Pαβ subunits and two inhibitory Pγ subunits. The Pγ subunits keep the enzyme ...
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Journal ArticleJ Biol Chem · December 15, 1992
In photoreceptor cells of vertebrates light activates a series of protein-protein interactions resulting in activation of a cGMP-phosphodiesterase (PDE). Interaction between the GTP-bound form of rod G-protein alpha-subunit (alpha t) and PDE inhibitory gam ...
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Journal ArticleBiomed Sci · March 1990
In order to study the role of individual amino acids in the function of the inhibitory subunit, gamma, of retinal rod phosphodiesterase (PDE), the following substitutions were made: Arg-24----Gly, Lys-29----Thr, Arg-33----Gly, Lys-39----Thr, Lys-41----Thr, ...
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Journal ArticleBioorg Khim · August 1989
Expression of the synthetic gene for human proinsulin in E. coli has been investigated. The proinsulin gene has been expressed directly under the control of a synthetic promoter of phage fd DNA and a promoter of tryptophan operon, or using fusions with fra ...
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Journal ArticleBioorg Khim · August 1986
The photoinduced covalent binding of E. coli RNA polymerase with decathymidylic templates containing 5-bromouracil residue has been carried out. Peptides from beta and beta' subunits of the core-enzyme, situated in the DNA-template binding site of the RNA ...
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Journal ArticleGene · November 1984
A chemical-enzymatic synthesis of 271- and 286-bp DNA duplexes, each of which contains the entire sequence coding for human proinsulin has been accomplished. In addition to the coding sequence, the 271-bp fragment carries translation initiation and termina ...
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