- DNA Repair Mechanisms
- Trace Elements in Health
- Cell death mechanisms and regulation
- Biocrusts and Microbial Ecology
- Cancer-related Molecular Pathways
- Mitochondrial Function and Pathology
- Chromium effects and bioremediation
- Bacterial Genetics and Biotechnology
- Iron Metabolism and Disorders
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Plant Genetic and Mutation Studies
- CRISPR and Genetic Engineering
- DNA and Nucleic Acid Chemistry
- Cancer therapeutics and mechanisms
- Bacterial biofilms and quorum sensing
- Porphyrin Metabolism and Disorders
- Advanced biosensing and bioanalysis techniques
- Algal biology and biofuel production
- RNA modifications and cancer
- Metal Extraction and Bioleaching
- PARP inhibition in cancer therapy
- Epigenetics and DNA Methylation
- Geology and Paleoclimatology Research
- ATP Synthase and ATPases Research
Indiana University School of Medicine
2020-2025
Indiana University – Purdue University Indianapolis
2020-2025
Indiana University
2024
University School
2024
University of Indianapolis
2023-2024
Indiana University Bloomington
2019-2022
University of Newcastle Australia
2014-2022
Members of the COG0523 subfamily candidate GTPase metallochaperones function in bacterial transition-metal homeostasis, but nature cognate metal, mechanism metal transfer, and identification target protein(s) for delivery remain open questions. Here, we explore multifunctionality members linked to delivering ZnII apoprotein targets under conditions host-imposed depletion. We examine two zinc-uptake repressor (Zur)-regulated family members, each from a major human pathogen, Acinetobacter...
Replication Protein A (RPA), a single-stranded DNA (ssDNA) binding protein, is vital for various aspects of genome maintenance such as replication, recombination, repair and cell cycle checkpoint activation. Binding RPA to ssDNA protects it from degradation by cellular nucleases, prevents secondary structure formation suppresses illegitimate recombination. In our current study, we identified the acetyltransferase p300 be capable acetylating 70kDa subunit in vitro within cells. The...
Replication protein A (RPA) is the major human single stranded DNA (ssDNA)-binding protein, playing essential roles in replication, repair, recombination, and DNA-damage response (DDR). Inhibition of RPA–DNA interactions represents a therapeutic strategy for cancer drug discovery has great potential to provide agent anticancer activity synergize with both common damaging chemotherapeutics newer targeted agents. In this letter, new series analogues based on our previously reported TDRL-551...
Transition metal homeostasis ensures that cells and organisms obtain sufficient to meet cellular demand while dispensing with any excess so as avoid toxicity. In bacteria, zinc restriction induces the expression of one or more Zur (zinc-uptake repressor)-regulated Cluster Orthologous Groups (COG) COG0523 proteins. proteins encompass a poorly understood sub-family G3E P-loop small GTPases, others which are known function metallochaperones in maturation cobalamin (CoII) NiII...
Poly (ADP-ribose) polymerase inhibitors (PARPi) are standard of care for many BRCA1 deficient cancers, though few cures achieved. We sought to determine if targeting the protection single-strand DNA gaps induced by PARPi in BRCA-deficient cancers could increase efficacy. Replication protein A (RPA) participates critical protein-protein and protein-DNA interactions protect single-stranded (ssDNA) support metabolism. have reported optimization small molecule RPA (RPAi) that target...
In response to bacterial infection, the vertebrate host employs metal-sequestering protein calprotectin (CP) withhold essential transition metals, notably Zn(II), inhibit growth. Previous studies of impact CP-imposed transition-metal starvation in
The ATR kinase responds to elevated levels of single-stranded DNA (ssDNA) activate the G2/M checkpoint, regulate origin utilization, preserve fork stability, and allow repair ensure genome integrity. intrinsic replication stress in cancer cells makes this pathway an attractive therapeutic target. ssDNA that drives signaling is sensed by ssDNA-binding protein A (RPA), which acts as a platform for ATRIP recruitment subsequent activation TopBP1. We have developed chemical RPA inhibitors (RPAi)...
Acinetobacter species are widely distributed bacteria in the environment, and have recently gained notoriety as opportunistic nosocomial pathogens. Here we characterize a novel RNA polymerase-interacting protein named acidic transcription factor A, AtfA. It is small highly acidic, throughout γ proteobacteria, including other significant pathogens genera Moraxella, Pseudomonas, Legionella Vibrio. In model A. baylyi ADP1, deletion of atfA significantly affects expression over 500 genes,...
Abstract The DNA Damage Response (DDR) is an integrated network of repair and cell signaling pathways that are critical towards maintaining genomic stability. most successful DDR targeted therapies inhibit the damage sensor, PARP, a protein recognizes single strand (ssDNA) breaks as well other secondary structures induced by gaps can initiate chromosome instability death. Building on initial clinical success PARP inhibitors, development therapeutics has become increasingly popular, however,...
ABSTRACT Replication Protein A (RPA), a single-stranded DNA (ssDNA) binding protein, is vital for various aspects of genome maintenance such as replication, recombination, repair and cell cycle checkpoint activation. Binding RPA to ssDNA protects it from degradation by cellular nucleases, prevents secondary structure formation illegitimate recombination. In our current study, we identified the acetyltransferase p300 be capable acetylating 70kDa subunit in vitro within cells. The acetylation...
The ATR kinase responds to elevated levels of single-stranded DNA (ssDNA) activate the G2/M checkpoint, regulate origin utilization, preserve fork stability, and allow repair towards ensuring genome integrity. intrinsic replication stress in cancer cells makes this pathway an attractive therapeutic target. ssDNA that drives signaling is sensed by ssDNA-binding protein A (RPA), which acts as a platform for ATRIP recruitment subsequent activation TopBP1. We have developed chemical RPA...
Summary Microbial palaeontology is largely reliant on the interpretation of geologically stable biomarkers or molecular fossils. Biomolecules that are both specific to particular groups organisms and a geological scale invaluable for tracing emergence diversification lifeforms, particularly in cases where mineral fossils lacking. 2‐Methylhopanoids their diagenic product, 2‐methylhopanes, highly abundant bacterial membrane lipids, recoverable from samples excess billion years old. In this...
Abstract Replication Protein A (RPA) is the major single-stranded DNA (ssDNA) binding protein in cell and plays a role replication, recombination, damage response (DDR) repair. RPA functions to protect ssDNA from degradation also serves as an interaction hub recruit replication DDR machinery. Under normal cellular conditions, abundance excess that of generated during S phase so fork collapse catastrophe event elevated levels stress. inhibition thus promising cancer therapeutic strategy...