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overview 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 TypeName
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 A bis-alkylating triplex forming oligonucleotide inhibits intracellular reporter gene expression and prevents triplex unwinding due to helicase activity.
Academic Article Displacement of a DNA binding protein by Dda helicase.
Academic Article DNA unwinding by Escherichia coli DNA helicase I (TraI) provides evidence for a processive monomeric molecular motor.
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 Analysis of the DNA translocation and unwinding activities of T4 phage helicases.
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 Dda helicase unwinds a DNA-PNA chimeric substrate: evidence for an inchworm mechanism.
Academic Article Structure and Mechanisms of SF1 DNA Helicases.
Academic Article Bacteriophage T4 Dda helicase translocates in a unidirectional fashion on single-stranded DNA.
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 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 Binding by the hepatitis C virus NS3 helicase partially melts duplex DNA.
Academic Article DNA unwinding and protein displacement by superfamily 1 and superfamily 2 helicases.
Academic Article Superfamily 2 helicases.
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 Kinetic mechanism for DNA unwinding by multiple molecules of Dda helicase aligned on DNA.
Academic Article Unwinding of unnatural substrates by a DNA helicase.
Academic Article Biotin-streptavidin-labeled oligonucleotides as probes of helicase mechanisms.
Academic Article A fluorescence-based assay for monitoring helicase activity.
Academic Article Protein displacement by helicases.
Concept DNA Helicases
Academic Article [G4-quadruplexes and genome instability].
Academic Article Kinetic Analysis of DNA Unwinding by E coli DNA Helicase l (Tral) reveals a highly Processive Monomeric Molecule Motor
Academic Article DNA Helicase Displaces Streptavidin from Biotin-Labeled Oligonucleotides with a 5'-to-3' Directional Bias
Academic Article DNA Unwinding by Escherichia coli DNA helicase l (Tral) Provides Evidence for a processive Monomeric Molecular Motor
Academic Article Chemical modifications of DNA for study of helicase mechanisms.
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 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 Protein-protein interaction analysis for functional characterization of helicases.
Academic Article Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA.
Academic Article Structure and function of Pif1 helicase.
Academic Article Pif1 helicase unfolding of G-quadruplex DNA is highly dependent on sequence and reaction conditions.
Grant Single molecule nucleic acid enzymology
Grant DNA Unwinding and Translocation by Helicases
Grant DNA Helicases: Mechanism and Function
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 Mitochondrial genetic variation is enriched in G-quadruplex regions that stall DNA synthesis in vitro.
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 Alignment of helicases on single-stranded DNA increases activity.

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  • DNA Helicases