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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	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	NS3 helicase from the hepatitis C virus can function as a monomer or oligomer depending on enzyme and substrate concentrations.
Academic Article	Helicase-catalysed translocation and strand separation.
Academic Article	Hepatitis C virus nonstructural protein 5A (NS5A) is an RNA-binding protein.
Academic Article	Phosphate release contributes to the rate-limiting step for unwinding by an RNA helicase.
Academic Article	Mechanisms: molecular machines.
Academic Article	RNA unwinding activity of the hepatitis C virus NS3 helicase is modulated by the NS5B polymerase.
Academic Article	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	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	Protein displacement by helicases.
Academic Article	Unwinding of nucleic acids by HCV NS3 helicase is sensitive to the structure of the duplex.
Concept	RNA, Fungal
Concept	RNA, Viral
Concept	RNA
Concept	DNA-Directed RNA Polymerases
Concept	RNA Viruses
Concept	RNA Helicases
Concept	RNA, Messenger
Concept	DEAD-box RNA Helicases
Concept	RNA-Binding Proteins
Concept	RNA, Double-Stranded
Concept	RNA, Catalytic
Academic Article	Mutation in the Putative Nuclear Localization Sequence of the Hepatitis C NS3 Protein Reduce Colony Formation After Transfection of HCV Replicon RNA into Huh 7 Cell
Academic Article	Peptide Nucleic Acid Inhibits HCV-Ns3 Catalyzed Unwinding of DNA and RNA Substrates
Academic Article	"RNA Helicases"
Academic Article	Identification of Protein Surfaces of NS3 that are Required for HCV Replication
Academic Article	Mutations in the Putative Nuclear Localization Sequence of the Hepatitis C NS3 Protein Conoly Formation after Transfection of HCV Replicon RNA into Huh 7 Cells
Academic Article	A CRISPR-based approach for proteomic analysis of a single genomic locus.
Academic Article	Probing RNA translocases with DNA.
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	Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress.
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	MOLECULAR PROBES FOR STUDYING TELOMERASE
Grant	Functions and Mechanisms of Helicases and G-Quadruplex Nucleic Acids
Grant	DNA Helicases: Mechanism and Function
Grant	MECHANISM OF THE RNA HELICASE OF THE HEPATITIS C VIRUS
Academic Article	DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA.
Academic Article	Identifying RNA Helicase Inhibitors Using Duplex Unwinding Assays.
Academic Article	G-quadruplex DNA inhibits unwinding activity but promotes liquid-liquid phase separation by the DEAD-box helicase Ded1p.
Academic Article	RNA helicases required for viral propagation in humans.
Academic Article	Hepatitis C virus nonstructural protein NS3 unfolds viral G-quadruplex RNA structures.
Academic Article	Alignment of helicases on single-stranded DNA increases activity.

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