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Raney, Kevin

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My laboratory is interested in the enzymology and chemistry of nucleic acid enzymes. Helicases are enzymes that manipulate DNA and RNA in all aspects of nucleic acid metabolism. We are studying a DNA helicase from Bacteriophage T4 called Dda (for DNA-Dependent-ATPase) in order to develop a detailed chemical and kinetic mechanism for DNA unwinding by this model DNA helicase. A second enzyme we study is called Pif1. This helicase is involved in many aspects of DNA metabolism ranging from telomere maintenance to transcription. Pif1 binds tightly to unusual DNA structures called quadruplexes, for which the biological functions are being intensively explored. A second project involves the Hepatitis C viral helicase NS3 (Non-Structural Protein 3). NS3 is an RNA helicase that is capable of unwinding DNA. We are studying the mechanism of NS3 as well as its interactions with other HCV and cellular proteins. Our goal is to recapitulate RNA replication in vitro using biological relevant substrates and proteins and a biologically relevant sub-genomic replicon of HCV. Our research projects are currently expanding in development of new tools for studying and protein-protein interactions and post-translational modifications at specific sites in the genome using a Crispr-based approach coupled with protein mass spectrometry. In a new project, we have recently discovered a possible signaling mechanism by which cells respond to DNA damage. During oxidative stress, guanine residues are oxidized, leading to excision of the damaged DNA. When the excised DNA consists of specific sequences containing runs of guanine, the resulting DNA fragment can fold into a stable structure called quadruplex DNA. Telomeric DNA is particularly susceptible to oxidative stress and contains sequences that readily fold into quadruplex structures. The excised DNA quadruplexes can bind to proteins such as DHX36 (a helicase), leading to formation of sub-organelles called stress granules. The functional role of stress granules is to modulate translation. Hence, this mechanism provides a stepwise chemical mechanism for the cell to respond to DNA damage leading to changes in translation.

One or more keywords matched the following items that are connected to Raney, Kevin

Item Type	Name
Academic Article	Chemically modified DNA substrates implicate the importance of electrostatic interactions for DNA unwinding by Dda helicase.
Academic Article	Intermediates revealed in the kinetic mechanism for DNA unwinding by a monomeric helicase.
Academic Article	Multiple full-length NS3 molecules are required for optimal unwinding of oligonucleotide DNA in vitro.
Academic Article	Structural and biological identification of residues on the surface of NS3 helicase required for optimal replication of the hepatitis C virus.
Academic Article	Displacement of a DNA binding protein by Dda helicase.
Academic Article	Purification and characterization of hepatitis C virus non-structural protein 5A expressed in Escherichia coli.
Academic Article	DNA unwinding by Escherichia coli DNA helicase I (TraI) provides evidence for a processive monomeric molecular motor.
Academic Article	NS3 helicase from the hepatitis C virus can function as a monomer or oligomer depending on enzyme and substrate concentrations.
Academic Article	Hepatitis C virus NS3 helicase forms oligomeric structures that exhibit optimal DNA unwinding activity in vitro.
Academic Article	The T4 phage SF1B helicase Dda is structurally optimized to perform DNA strand separation.
Academic Article	Investigation of translocation, DNA unwinding, and protein displacement by NS3h, the helicase domain from the hepatitis C virus helicase.
Academic Article	Dda helicase tightly couples translocation on single-stranded DNA to unwinding of duplex DNA: Dda is an optimally active helicase.
Academic Article	Structure and Mechanisms of SF1 DNA Helicases.
Academic Article	Increasing the length of the single-stranded overhang enhances unwinding of duplex DNA by bacteriophage T4 Dda helicase.
Academic Article	Helicase-catalysed translocation and strand separation.
Academic Article	Stoichiometry and DNA unwinding by the bacteriophage T4 41:59 helicase.
Academic Article	Hepatitis C virus nonstructural protein 5A (NS5A) is an RNA-binding protein.
Academic Article	Hepatitis C virus non-structural protein 3 (HCV NS3): a multifunctional antiviral target.
Academic Article	Phosphate release contributes to the rate-limiting step for unwinding by an RNA helicase.
Academic Article	Non-Watson-Crick interactions between PNA and DNA inhibit the ATPase activity of bacteriophage T4 Dda helicase.
Academic Article	Mechanisms: molecular machines.
Academic Article	Bacteriophage T4 Dda helicase translocates in a unidirectional fashion on single-stranded DNA.
Academic Article	Novel, fluorescent, SSB protein chimeras with broad utility.
Academic Article	Measurement of steady-state kinetic parameters for DNA unwinding by the bacteriophage T4 Dda helicase: use of peptide nucleic acids to trap single-stranded DNA products of helicase reactions.
Academic Article	Protein displacement by an assembly of helicase molecules aligned along single-stranded DNA.
Academic Article	RNA unwinding activity of the hepatitis C virus NS3 helicase is modulated by the NS5B polymerase.
Academic Article	DNA helicases displace streptavidin from biotin-labeled oligonucleotides.
Academic Article	Evidence for a functional monomeric form of the bacteriophage T4 DdA helicase. Dda does not form stable oligomeric structures.
Academic Article	DNA unwinding and protein displacement by superfamily 1 and superfamily 2 helicases.
Academic Article	Modulation of the hepatitis C virus RNA-dependent RNA polymerase activity by the non-structural (NS) 3 helicase and the NS4B membrane protein.
Academic Article	AAV-2 Rep78 and HPV-16 E1 interact in vitro, modulating their ATPase activity.
Academic Article	Development and evaluation of a structural model for SF1B helicase Dda.
Academic Article	Yeast Pif1 helicase exhibits a one-base-pair stepping mechanism for unwinding duplex DNA.
Academic Article	Hepatitis C virus nonstructural protein 5A: biochemical characterization of a novel structural class of RNA-binding proteins.
Academic Article	Unwinding of unnatural substrates by a DNA helicase.
Academic Article	A fluorescence-based assay for monitoring helicase activity.
Academic Article	Protein displacement by helicases.
Academic Article	Unwinding of nucleic acids by HCV NS3 helicase is sensitive to the structure of the duplex.
Concept	Bacterial Proteins
Concept	DNA-Binding Proteins
Concept	Oncogene Proteins, Viral
Concept	Luminescent Proteins
Concept	Molecular Motor Proteins
Concept	Repressor Proteins
Concept	Recombinant Proteins
Concept	Mitochondrial Proteins
Concept	Escherichia coli Proteins
Concept	Viral Proteins
Concept	Saccharomyces cerevisiae Proteins
Concept	RNA-Binding Proteins
Concept	Viral Nonstructural Proteins
Concept	Proto-Oncogene Proteins c-kit
Concept	Recombinant Fusion Proteins
Concept	Telomere-Binding Proteins
Academic Article	Identification of Protein-protein Interactions among Non-Structural Proteins from HCV and Evidence for a Dominant-Negative Effect of an ATPase-deficient mutant of NS3
Academic Article	A CRISPR-based approach for proteomic analysis of a single genomic locus.
Academic Article	Simultaneous binding to the tracking strand, displaced strand and the duplex of a DNA fork enhances unwinding by Dda helicase.
Academic Article	Yeast Pif1 accelerates annealing of complementary DNA strands.
Academic Article	A parallel quadruplex DNA is bound tightly but unfolded slowly by pif1 helicase.
Academic Article	XLPM: efficient algorithm for the analysis of protein-protein contacts using chemical cross-linking mass spectrometry.
Academic Article	Yeast transcription co-activator Sub1 and its human homolog PC4 preferentially bind to G-quadruplex DNA.
Academic Article	Melting of Duplex DNA in the Absence of ATP by the NS3 Helicase Domain through Specific Interaction with a Single-Strand/Double-Strand Junction.
Academic Article	Yeast Helicase Pif1 Unwinds RNA:DNA Hybrids with Higher Processivity than DNA:DNA Duplexes.
Academic Article	The Yeast Mitochondrial RNA Polymerase and Transcription Factor Complex Catalyzes Efficient Priming of DNA Synthesis on Single-stranded DNA.
Academic Article	Analysis of Protein-protein Interaction Interface between Yeast Mitochondrial Proteins Rim1 and Pif1 Using Chemical Cross-linking Mass Spectrometry.
Academic Article	Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA.
Academic Article	A biochemical and biophysical model of G-quadruplex DNA recognition by positive coactivator of transcription 4.
Academic Article	A catch and release program for single-stranded DNA.
Academic Article	Structure and function of Pif1 helicase.
Academic Article	N-Naphthoyl-substituted indole thio-barbituric acid analogs inhibit the helicase activity of the hepatitis C virus NS3.
Grant	Mechanisms of RNA binding and remodeling proteins
Grant	HCV NS3: Biological, Biochemical and Structural Analysis
Grant	HCV NS3 and NS5A: Biochemical Mechanisms and Biological Functions
Grant	MECHANISM OF HEPACIVIRUS REPLICASE ASSEMBLY
Grant	G-quadruplex DNA as a chemical signaling agent
Grant	Functions and Mechanisms of Helicases and G-Quadruplex Nucleic Acids
Grant	DNA Helicases: Mechanism and Function
Academic Article	DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA.
Academic Article	Direct quantification of the translocation activities of Saccharomyces cerevisiae Pif1 helicase.
Academic Article	Structural basis for DNA unwinding at forked dsDNA by two coordinating Pif1 helicases.
Academic Article	G-Quadruplex loops regulate PARP-1 enzymatic activation.
Academic Article	G-quadruplex DNA inhibits unwinding activity but promotes liquid-liquid phase separation by the DEAD-box helicase Ded1p.
Academic Article	A structural feature of Dda helicase which enhances displacement of streptavidin and trp repressor from DNA.
Academic Article	Hepatitis C virus nonstructural protein NS3 unfolds viral G-quadruplex RNA structures.
Academic Article	Pif1 Helicase Mediates Remodeling of Protein-Nucleic Acid Complexes by Promoting Dissociation of Sub1 from G-Quadruplex DNA and Cdc13 from G-Rich Single-Stranded DNA.

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