A5064820122- RNA regulation and disease
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- DNA and Nucleic Acid Chemistry
- Viral Infections and Immunology Research
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Bacteriophages and microbial interactions
- Sulfur-Based Synthesis Techniques
- interferon and immune responses
- Biochemical and Molecular Research
- Nanoplatforms for cancer theranostics
- Synthesis and Characterization of Heterocyclic Compounds
- Virus-based gene therapy research
- Enzyme Structure and Function
- Cytomegalovirus and herpesvirus research
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- Immune Response and Inflammation
- Pneumocystis jirovecii pneumonia detection and treatment
University of California, Davis
2016-2025
University of California System
2017-2022
University of California, San Diego
2015
California Institute of Technology
1991-2010
University of Utah
2000-2009
Howard Hughes Medical Institute
2004
Harvard University
2000
Harvard University Press
1995
Purdue University West Lafayette
1992
Grand Forks Air Force Base
1989
Relative orientations of the DNA strands within a purine⋅purine⋅pyrimidine triple helix have been determined by affinity cleaving. A purine-rich oligonucleotide bound in major groove double-helical antiparallel to Watson-Crick purine strand. Binding depended upon concentration multivalent cations such as spermine or Mg 2+ , and appeared be relatively independent pH. Two models with specific hydrogen-bonding patterns for base triplets (G⋅GC, A⋅AT, T⋅AT) are proposed explain sequence...
CRISPR-Cas-guided base editors convert A•T to G•C, or C•G T•A, in cellular DNA for precision genome editing. To understand the molecular basis adenosine deamination by adenine (ABEs), we determined a 3.2-angstrom resolution cryo-electron microscopy structure of ABE8e substrate-bound state which deaminase domain engages exposed within CRISPR-Cas9 R-loop complex. Kinetic and structural data suggest that catalyzes up ~1100-fold faster than earlier ABEs because mutations stabilize substrates...
The FKBP12-rapamycin associated protein (FRAP, also RAFT, mTOR) belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses stresses such as DNA damage and nutrient deprivation in variety eukaryotes from yeast humans. FRAP regulates G<sub>1</sub>cell cycle progression translation initiation part by controlling the phosphorylation states number translational cell regulators. Although is known be phosphorylated<i>in vivo</i> phosphorylate...
Editing of the pre-mRNA for DNA repair enzyme NEIL1 causes a lysine to arginine change in lesion recognition loop protein. The two forms are shown here have distinct enzymatic properties. edited form removes thymine glycol from duplex 30 times more slowly than encoded genome, whereas editing enhances guanidinohydantoin by NEIL1. In addition, we show that recoding site is preferred RNA adenosine deaminase ADAR1. resides an A-C mismatch hairpin stem formed pairing exon 6 immediate upstream...
Adenosine deaminases that act on RNA (ADARs) carry out adenosine (A) to inosine (I) editing reactions with a known requirement for duplex RNA. Here, we show ADARs also react DNA/RNA hybrid duplexes. Hybrid substrates are deaminated efficiently by ADAR deaminase domains at dA-C mismatches and E Q mutations in the base flipping loop of enzyme. For long, perfectly matched hybrid, deamination is more efficient full length ADAR2 than its isolated domain. Guide strands directed DNA were used...
Abstract Adenosine deaminases acting on RNA (ADARs) are enzymes that convert adenosine to inosine in duplex RNA, a modification exhibits multitude of effects structure and function. Recent studies have identified ADAR1 as potential cancer therapeutic target. ADARs also important the development directed editing therapeutics. A comprehensive understanding molecular mechanism ADAR reaction will advance efforts develop inhibitors new tools for editing. Here we report X-ray crystal fragment...
The innate immune system relies on molecular sensors to detect distinctive patterns, including viral double-stranded RNA (dsRNA), which triggers responses resulting in apoptosis and infiltration. Adenosine Deaminases Acting (ADARs) catalyze the deamination of adenosine (A) inosine (I), serving as a mechanism distinguish self from non-self prevent aberrant activation. Loss-of-function mutations ADAR1 gene are one cause Aicardi Goutières Syndrome (AGS), severe autoimmune disorder children....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRecognition of all four base pairs double-helical DNA by triple-helix formation: design nonnatural deoxyribonucleosides for pyrimidine.cntdot.purine pair bindingLinda C. Griffin, Laura L. Kiessling, Peter A. Beal, Paul Gillespie, and B. DervanCite this: J. Am. Chem. Soc. 1992, 114, 21, 7976–7982Publication Date (Print):October 1, 1992Publication History Published online1 May 2002Published inissue 1 October...
Journal Article The influence of single base triplet changes on the stability a Pur·Pur·Pyr triple helix determined by affinity cleaving Get access Peter A. Beal, Beal Arnold and Mabel Beckman Laboratories Chemical Synthesis, California Institute TechnologyPasadena, CA 91125, USA Search for other works this author on: Oxford Academic PubMed Google Scholar B. Dervan * To whom correspondence should be addressed Nucleic Acids Research, Volume 20, Issue 11, 11 June 1992, Pages 2773–2776,...
Immune stimulation is a significant hurdle in the development of effective and safe RNA interference therapeutics. Here, we address this problem context mimic microRNA-122 by employing novel nucleobase known 2'-ribose modifications. The modifications are analogues adenosine guanosine that contain cyclopentyl propyl minor-groove projections. Via site-by-site chemical modification analysis, identify several immunostimulatory 'hot spots' within miRNA guide strand at which single base...
The analytical identification of positional isomers (e.g., 3-, N4-, 5-methylcytidine) within the > 160 different post-transcriptional modifications found in RNA can be challenging. Conventional liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) approaches rely on chromatographic separation for accurate because collision-induced dissociation (CID) spectra these nearly exclusively yield identical nucleobase ions (BH2+) from same molecular ion (MH+). Here, we have explored...
Adenosine deamination is one of the most prevalent post-transcriptional modifications in mRNA and catalyzed by ADAR1 ADAR2 humans. have different substrate selectivity, which believed to mainly originate from proteins' deaminase domains (hADAR1d hADAR2d, respectively). RNA-seq Saccharomyces cerevisiae transcriptome subjected ADAR-catalyzed RNA editing identified substrates with common secondary structure features preferentially edited hADAR1d over hADAR2d. The relatively small size efficient...
ADARs (adenosine deaminases acting on RNA) can be directed to sites in the transcriptome by complementary guide strands allowing for correction of disease-causing mutations at RNA level. However, show bias against editing adenosines with a guanosine 5' nearest neighbor (5'-GA sites), limiting scope this approach. Earlier studies suggested effect arises from clash minor groove involving 2-amino group adjacent an site. Here we that nucleosides capable pairing syn conformation enhance 5'-GA...
Adenosine deaminases acting on RNA (ADARs) are editing enzymes that catalyze the hydrolytic deamination of adenosine (A) to inosine (I) in dsRNA. In humans, two catalytically active ADARs, ADAR1 and ADAR2, perform this A-to-I event. The growing field nucleotide base has highlighted ADARs as promising therapeutic agents while multiple studies have also identified ADAR1's role cancer progression. However, potential for site-directed well rational design inhibitors is being hindered by lack...