Adozelesin is a synthetic analog of the antitumor antibiotic, CC-1065, which alkylates N3 of adenine in the minor DNA groove in a sequence-specific manner. Here we tested the mutation spectra induced by adozelesin in the supF gene of human XP-A fibroblasts using a shuttle vector assay. Adozelesin primarily induces mutations via an A --> T transversion and a single base insertion. The A --> T transversion (43/59) was observed at the adenine alkylation site in the 5'-ATTTA* sequence (A* is the site of alkylation). The single base insertion (5/59) was observed at the 3'-side of the covalently modified adenine in the 5'-CTAAA* sequence. The results of this study suggest that the DNA alkylating sequence of adozelesin influences the type of DNA mutation.
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http://dx.doi.org/10.1007/s12272-010-0419-7 | DOI Listing |
Int J Mol Sci
January 2025
Departamento de Micro y Nanotecnologías, Instituto de Ciencias Aplicadas y Tecnología, Universidad Nacional Autónoma de México, Cto. Exterior S/N, C.U., Coyoacán, Ciudad de México C.P. 04510, Mexico.
Thermus thermophilus HB27 laccase (Tth-Lac) is a thermostable enzyme that contains a β-hairpin (Ala292-Gln307) covering the substrate entrance. We analyzed the role of this β-hairpin in the enzymatic activity of Tth-Lac through three β-hairpin mutants: two variants without the β-hairpin (C1Tth-Lac and C2Tth-Lac) and one with a partially modified β-hairpin (P1Tth-Lac). Enzymatic activity was assayed with different substrates with and without copper.
View Article and Find Full Text PDFMutat Res Genet Toxicol Environ Mutagen
January 2025
Free University of Berlin, Institute of Pharmacy, Pharmacology and Toxicology, Berlin, Germany; BASF SE, Experimental Toxicology and Ecology, Ludwigshafen am Rhein, Germany.
Mutagenicity testing is a component of the hazard assessment of industrial chemicals, biocides, and pesticides. Mutations induced by test substances can be detected by in vitro and in vivo methods that have been adopted as OECD Test Guidelines. One of these in vivo methods is the Transgenic Rodent Assay (TGRA), OECD test guideline no.
View Article and Find Full Text PDFNPJ Antimicrob Resist
March 2024
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Comprehensive knowledge of mechanisms driving the acquisition of antimicrobial resistance is essential for the development of new drugs with minimized resistibility. To gain this knowledge, we combine experimental evolution in a continuous culturing device, the morbidostat, with whole genome sequencing of evolving cultures followed by characterization of drug-resistant isolates. Here, this approach was used to assess evolutionary dynamics of resistance acquisition against DNA gyrase/topoisomerase TriBE inhibitor GP6 in Escherichia coli and Acinetobacter baumannii.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
Intermolecular hydrogen bonds between carboxyl (COO) and amino groups are a common weak interaction in proteins. Infrared (IR) spectral assignment of such an intermolecular hydrogen bond provides a fingerprint for studying protein-protein interactions as its absorption frequency is affected by the molecular electrostatic environment. Temperature-dependent FTIR and temperature-jump time-resolved IR absorbance difference spectra of several typical amino acids and those of wild type and single-site mutated αB-crystallin were performed.
View Article and Find Full Text PDFJ Neurodev Disord
January 2025
Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Boston Children's Hospital, Brookline, MA, USA.
Background: Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations.
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