A5058308706- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Marine Sponges and Natural Products
- Crystallography and molecular interactions
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Bacterial Genetics and Biotechnology
- Synthesis and Characterization of Pyrroles
- RNA regulation and disease
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Microbial Natural Products and Biosynthesis
- Coral and Marine Ecosystems Studies
- Marine and coastal plant biology
- Immune Response and Inflammation
- Seaweed-derived Bioactive Compounds
- Protein Degradation and Inhibitors
- Marine Biology and Environmental Chemistry
- Polyomavirus and related diseases
The University of Texas at Austin
2021-2024
University of South Florida
2016-2023
New York State Office for People With Developmental Disabilities
1989
Abstract The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates cells are not fully delineated. Here proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show binding to R-loops and vitro. Genetic demonstrate increases lacking decreases overexpressing APOBEC3B. Genome-wide analyses major changes the overall landscape physiological stimulus-induced thousands...
Abstract Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression cell fate. Here we show that neddylation promotes SG assembly response to arsenite-induced oxidative stress. Inhibition or depletion of key components the machinery concomitantly inhibits stress-induced polysome disassembly assembly. Affinity purification subsequent mass-spectrometric analysis Nedd8-conjugated proteins from ribosomal fractions...
Timely stalling and resumption of RNA polymerases at damaged chromatin are actively regulated processes. Prior work showed an importance FACT histone chaperone in such process. Here we provide a new role OTUD5 deubiquitinase the FACT-dependent Through DUB RNAi screen, found as specific stabilizer UBR5 E3 ligase. localizes to DNA double strand breaks (DSBs), interacts with represses Pol II elongation synthesis. co-localizes component SPT16 antagonizes H2A deposition DSB lesions. independently...
Significance The BMI1-containing Polycomb Repressive Complex is an important gene silencer during development, stem cell maintenance, and cancer progression. BMI1 also involved in DNA damage response, but its downstream mechanism unclear. Here we identified UBR5 as a factor whose chromatin recruitment regulated by BMI1. We showed that repress the RNA polymerase II (Pol II) elongation nascent synthesis at UV-induced lesions. associates with regulates abundance of histone chaperon complex FACT...
The histone demethylase KDM5A erases H3 lysine 4 methylation, which is involved in transcription and DNA damage responses (DDRs). While DDR functions of have been identified, how recognizes lesion sites within chromatin unknown. Here, we identify two factors that act upstream to promote its association with sites. We identified a noncanonical poly(ADP-ribose) (PAR)–binding region unique KDM5A. Loss the PAR-binding or treatment PAR polymerase (PARP) inhibitors (PARPi’s) blocks KDM5A–PAR...
Abstract We have studied the effects of specific amino acid replacements in EF-Tu upon protein's interactions with guanine nucleotides and elongation factor Ts (EFTs). found that alterations at lysine residue Asn-Lys-Cys-Asp sequence, ring-binding differentially affect ability to bind nucleotides. Wild type (Lys-136) binds GDP GTP much more tightly than do many altered proteins. Replacing by arginine lowers affinity for about 20-fold relative change its EF-Ts. Substitutions 136 glutamine...
Common fragile sites (CFSs) are breakage-prone genomic loci, and considered to be hotspots for rearrangements frequently observed in cancers. Understanding the underlying mechanisms CFS instability will lead better insight on cancer etiology. Here we show that Polycomb group proteins BMI1 RNF2 suppressors of transcription-replication conflicts (TRCs) instability. Cells depleted or showed slower replication forks elevated fork stalling. These phenotypes associated with increase occupancy RNA...
The subtidal red alga Plocamium cartilagineum was collected from the Western Antarctic Peninsula during 2011 and 2017 austral summers. Bulk collections specific sites corresponded to chemogroups identified by Young et al. in 2013. One of yielded several known acyclic halogenated monoterpenes (2-5) as well undescribed compounds same class, anverenes B-D (6-8). Examination another chemogroup an cyclic monoterpene anverene E (9) its major secondary metabolite. Elucidation structures achieved...
An Antarctic coral belonging to the order Pennatulacea, collected during 2013 austral autumn by trawl from 662 944 m depth, has yielded three new briarane diterpenes, bathyptilone A-C (1–3) along with a trinorditerpene, enbepeanone A (4), which bears carbon skeleton. Structure elucidation was facilitated one- and two-dimensional NMR spectroscopy, mass spectrometry confirmed X-ray crystallography. The compounds were screened in four cancer cell lines. Bathyptilone displayed selective...
Abstract Proper regulation of replication fork progression is important for genomic maintenance. Subverting the transcription-induced conflicts crucial in preserving integrity forks. Various chromatin remodelers, such as histone chaperone and deacetylases are known to modulate stress, but how these factors organized or collaborate not well understood. Here we found a new role OTUD5 deubiquitinase limiting stress. We that recruited forks, its depletion causes Through C-terminal disordered...
Sponges are at the forefront of marine natural product research. In deep sea, extreme conditions have driven secondary metabolite pathway evolution such that we might expect deep-sea sponges to yield a broad range unique products. Here, investigate chemodiversity tetractinellid sponge, Characella pachastrelloides, collected from ~800 m depth in Irish waters. First, analyzed MS/MS data obtained fractions this sponge on GNPS public online platform guide our exploration its chemodiversity....
Diamond Blackfan anemia (DBA) is caused by germline heterozygous loss-of-function pathogenic variants (PVs) in ribosomal protein (RP) genes, most commonly
Abstract Common fragile sites (CFSs) are breakage-prone genomic loci, and considered to be hotspots for rearrangements frequently observed in cancers. Understanding the underlying mechanisms CFS instability will lead better insight on cancer etiology. Here we show that Polycomb group proteins BMI1 RNF2 suppressors of transcription-replication conflicts (TRCs) instability. Cells depleted or showed slower replication forks elevated fork stalling. These phenotypes associated with increase...