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Eoff, Robert

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The research I pursue is focused on DNA replication and seeks to provide fundamental insights into how these mechanisms are related to human health, especially cancer. I have expertise in a number of areas pertinent to the current application including: biochemical/biophysical analysis of enzymes, structural biology (X-ray crystallography and molecular modeling techniques), mass spectrometry and genomic instability in cancer. In addition to in silico modeling approaches, I have been involved in solving thirty-four crystal structures submitted to the Protein Data Bank. I am first author on seventeen of these PDB submissions, and my laboratory has solved five crystal structures since I joined the faculty at UAMS. I have an active collaboration (General users proposal, GUP-41183) with the Northeastern collaborative access team (NE-CAT) at the Advanced Photon Source (APS) that grants us access to the 24-ID-E and 24-ID-C beamlines for data collection. The research I pursue is focused on DNA damage tolerance pathways and seeks to provide fundamental insights into how these mechanisms function under basal conditions and how they go astray during tumorigenesis or as a function of age. I have received funding from the National Institutes of Health in the form of an R00 award (GM084460) and a R01 (CA183895). I have established a strong research program with two senior post-doctoral fellows and three Ph.D. students. In less than four years, my team has published nine full, peer-reviewed research articles on which I am corresponding author. Work from my group has recently culminated in a manuscript that reveals important and previously unrecognized properties related to Werner’s syndrome protein (WRN) modulation of polymerase activity during bypass of oxidative DNA damage. Experiments from my group illustrate that WRN has a strong impact on the DNA adduct bypass properties of human DNA polymerases (pols) eta and kappa, inducing more accurate synthesis across oxidative damage (published in The Journal of Biological Chemistry and Nucleic Acids Research). Another study from my laboratory that was conducted in collaboration with Prof. Peter Crooks (UAMS) identified novel small-molecule inhibitors of the replication stress response enzyme human DNA polymerase eta, with the resulting manuscript recently being published in ACS Chemical Biology. We continue to pursue projects related to translesion polymerase activity in cancer and are actively developing new TLS pol inhibitors as a way to sensitize tumors to genotoxic anti-cancer drugs (e.g. cisplatin, doxorubicin). My long-term goal is to contribute in a meaningful fashion to the scientific endeavors that seek to improve human health, our ability to treat disease & our fundamental understanding of living systems.

One or more keywords matched the following items that are connected to Eoff, Robert

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	Hydrogen bonding of 7,8-dihydro-8-oxodeoxyguanosine with a charged residue in the little finger domain determines miscoding events in Sulfolobus solfataricus DNA polymerase Dpo4.
Academic Article	DNA unwinding by Escherichia coli DNA helicase I (TraI) provides evidence for a processive monomeric molecular motor.
Academic Article	Molecular basis of selectivity of nucleoside triphosphate incorporation opposite O6-benzylguanine by sulfolobus solfataricus DNA polymerase Dpo4: steady-state and pre-steady-state kinetics and x-ray crystallography of correct and incorrect pairing.
Academic Article	Calcium is a cofactor of polymerization but inhibits pyrophosphorolysis by the Sulfolobus solfataricus DNA polymerase Dpo4.
Academic Article	Conformational changes during nucleotide selection by Sulfolobus solfataricus DNA polymerase Dpo4.
Academic Article	A conformational transition in the structure of a 2'-thiomethyl-modified DNA visualized at high resolution.
Academic Article	Translesion DNA synthesis by human DNA polymerase eta on templates containing a pyrimidopurinone deoxyguanosine adduct, 3-(2'-deoxy-beta-d-erythro-pentofuranosyl)pyrimido-[1,2-a]purin-10(3H)-one.
Academic Article	Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage.
Academic Article	Enhancement of human DNA polymerase ? activity and fidelity is dependent upon a bipartite interaction with the Werner syndrome protein.
Academic Article	Roles of the four DNA polymerases of the crenarchaeon Sulfolobus solfataricus and accessory proteins in DNA replication.
Academic Article	Structural and functional analysis of Sulfolobus solfataricus Y-family DNA polymerase Dpo4-catalyzed bypass of the malondialdehyde-deoxyguanosine adduct.
Academic Article	Structure-function relationships in miscoding by Sulfolobus solfataricus DNA polymerase Dpo4: guanine N2,N2-dimethyl substitution produces inactive and miscoding polymerase complexes.
Academic Article	In vitro bypass of the major malondialdehyde- and base propenal-derived DNA adduct by human Y-family DNA polymerases ?, ?, and Rev1.
Academic Article	Dda helicase unwinds a DNA-PNA chimeric substrate: evidence for an inchworm mechanism.
Academic Article	A nucleotide-analogue-induced gain of function corrects the error-prone nature of human DNA polymerase iota.
Academic Article	Leukotriene biosynthesis inhibitor MK886 impedes DNA polymerase activity.
Academic Article	Modulation of the structure, catalytic activity, and fidelity of African swine fever virus DNA polymerase X by a reversible disulfide switch.
Academic Article	N-Aroyl indole thiobarbituric acids as inhibitors of DNA repair and replication stress response polymerases.
Academic Article	Selective modulation of DNA polymerase activity by fixed-conformation nucleoside analogues.
Academic Article	Metal-ion dependence of the active-site conformation of the translesion DNA polymerase Dpo4 from Sulfolobus solfataricus.
Academic Article	Structural and functional elucidation of the mechanism promoting error-prone synthesis by human DNA polymerase kappa opposite the 7,8-dihydro-8-oxo-2'-deoxyguanosine adduct.
Academic Article	Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes.
Academic Article	Replication, repair, and translesion polymerase bypass of N6-oxopropenyl-2'-deoxyadenosine.
Academic Article	Structure and activity of Y-class DNA polymerase DPO4 from Sulfolobus solfataricus with templates containing the hydrophobic thymine analog 2,4-difluorotoluene.
Academic Article	Differential furanose selection in the active sites of archaeal DNA polymerases probed by fixed-conformation nucleotide analogues.
Academic Article	Kinetic mechanism for DNA unwinding by multiple molecules of Dda helicase aligned on DNA.
Academic Article	Sulfolobus solfataricus DNA polymerase Dpo4 is partially inhibited by "wobble" pairing between O6-methylguanine and cytosine, but accurate bypass is preferred.
Academic Article	Mechanism of nucleic acid unwinding by SARS-CoV helicase.
Academic Article	Versatility of Y-family Sulfolobus solfataricus DNA polymerase Dpo4 in translesion synthesis past bulky N2-alkylguanine adducts.
Academic Article	A comprehensive strategy to discover inhibitors of the translesion synthesis DNA polymerase ?.
Academic Article	Kinetic analysis of base-pairing preference for nucleotide incorporation opposite template pyrimidines by human DNA polymerase iota.
Concept	DNA Damage
Concept	DNA, Bacterial
Concept	DNA Polymerase I
Concept	DNA Polymerase III
Concept	DNA Replication
Concept	DNA, Viral
Concept	DNA-Directed DNA Polymerase
Concept	DNA Repair
Concept	DNA Polymerase II
Concept	DNA-Binding Proteins
Concept	DNA, Mitochondrial
Concept	DNA Helicases
Concept	DNA
Concept	DNA Breaks, Double-Stranded
Concept	DNA Mismatch Repair
Concept	DNA Primers
Concept	DNA Primase
Concept	Uracil-DNA Glycosidase
Concept	DNA, Single-Stranded
Concept	DNA Repair Enzymes
Concept	DNA End-Joining Repair
Concept	DNA Polymerase beta
Concept	DNA, Archaeal
Concept	DNA Adducts
Academic Article	Human Rev1 polymerase disrupts G-quadruplex DNA.
Academic Article	Springer, New York, USA: Trevor Penning; Chemical Carcinogenesis: Bypass DNA polymerases
Academic Article	Wiley-VCH, Weinheim, Germany: Geacintov, N. E. & Broyde, S. (eds); 2010. Impact of Chemical Adducts on Translesion Synthesis in Replicative and Bypass DNA Polymerases: From Structure to Function
Academic Article	Elucidation of kinetic mechanisms of human translesion DNA polymerase ? using tryptophan mutants.
Academic Article	The Werner syndrome protein limits the error-prone 8-oxo-dG lesion bypass activity of human DNA polymerase kappa.
Academic Article	Biochemical analysis of six genetic variants of error-prone human DNA polymerase ? involved in translesion DNA synthesis.
Academic Article	Kinetic analysis of human PrimPol DNA polymerase activity reveals a generally error-prone enzyme capable of accurately bypassing 7,8-dihydro-8-oxo-2'-deoxyguanosine.
Academic Article	Evidence for the kinetic partitioning of polymerase activity on G-quadruplex DNA.
Academic Article	Kynurenine Signaling Increases DNA Polymerase Kappa Expression and Promotes Genomic Instability in Glioblastoma Cells.
Academic Article	Effects of Twelve Germline Missense Variations on DNA Lesion and G-Quadruplex Bypass Activities of Human DNA Polymerase REV1.
Academic Article	Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress.
Academic Article	Aberrant Kynurenine Signaling Modulates DNA Replication Stress Factors and Promotes Genomic Instability in Gliomas.
Academic Article	Human Translesion Polymerase ? Exhibits Enhanced Activity and Reduced Fidelity Two Nucleotides from G-Quadruplex DNA.
Academic Article	Residues in the RecQ C-terminal Domain of the Human Werner Syndrome Helicase Are Involved in Unwinding G-quadruplex DNA.
Academic Article	A catch and release program for single-stranded DNA.
Academic Article	Translesion DNA Synthesis in Cancer: Molecular Mechanisms and Therapeutic Opportunities.
Academic Article	A Small-Molecule Inhibitor of Human DNA Polymerase ? Potentiates the Effects of Cisplatin in Tumor Cells.
Grant	Translesion Synthesis Opposite Carcinogen Bound DNA
Grant	Coordinating Translesion DNA Synthesis Opposite Damaged DNA
Grant	Coordinating Translesion DNA Synthesis Opposite Damaged DNA
Grant	Translesion DNA polymerase kappa activity in gliomas
Grant	G-quadruplex DNA as a chemical signaling agent
Grant	Functions and Mechanisms of Helicases and G-Quadruplex Nucleic Acids
Academic Article	LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation.
Academic Article	Inhibition of Human DNA Polymerases Eta and Kappa by Indole-Derived Molecules Occurs through Distinct Mechanisms.
Grant	Replication of G-quadruplex DNA by translesion polymerases
Academic Article	A Facile Semisynthesis and Evaluation of Garcinoic Acid and Its Analogs for the Inhibition of Human DNA Polymerase ?.
Academic Article	Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs.
Grant	Mechanistic characterization of the cell cycle-dependent DNA repair pathway- Resubmission
Academic Article	Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells.
Academic Article	Site-Specific Synthesis of Oligonucleotides Containing 6-Oxo-M1dG, the Genomic Metabolite of M1dG, and Liquid Chromatography-Tandem Mass Spectrometry Analysis of Its In Vitro Bypass by Human Polymerase ?.
Academic Article	Conservation of the insert-2 motif confers Rev1 from different species with an ability to disrupt G-quadruplexes and stimulate translesion DNA synthesis.

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