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Guanine-rich DNA sequences can fold into non-canonical nucleic acid structures called G-quadruplexes (G4s). These nanostructures have strong implications in many fields, from medical science to bottom-up nanotechnologies. As a result, ligands interacting with G4s have attracted great attention as candidates in medical therapies, molecular probe applications, and biosensing. In recent years, the use of G4-ligand complexes as photopharmacological targets has shown significant promise for developing novel therapeutic strategies and nanodevices. Here, we studied the possibility of manipulating the secondary structure of a human telomeric G4 sequence through the interaction with two photosensitive ligands, DTE and TMPyP4, whose response to visible light is different. The effect of these two ligands on G4 thermal unfolding was also considered, revealing the occurrence of peculiar multi-step melting pathways and the different attitudes of the two molecules on the quadruplex stabilization.
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http://dx.doi.org/10.3390/ijms24109090 | DOI Listing |
Biochemistry
September 2025
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, United States.
SAMHD1 (SAM domain and HD domain-containing protein 1) is a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) with functions in viral restriction, R-loop resolution, DNA repair, telomere maintenance, ssRNA homeostasis, and regulation of self-nucleic acids. As a dNTPase, SAMHD1 functions as an allosterically activated tetramer, where binding of GTP to the A1 activator site of each monomer initiates dNTP-dependent tetramerization. cEM structures reveal that the nucleic-acid-related functions of SAMHD1 involve binding of guanine residues to the A1 site, leading to oligomeric forms that appear as beads-on-a-string on single-stranded RNA and DNA.
View Article and Find Full Text PDFAm J Hum Biol
September 2025
University of California, San Francisco, San Francisco, California, USA.
Background: Telomere length (TL) is a valuable marker of aging and stress that reflects both genetic and environmental influences. Quantitative PCR (qPCR) TL measurement is a powerful and cost-effective assay, especially in population studies with limited quantities of source material. Nevertheless, collecting and transporting high-quality blood samples can be logistically challenging, and research suggests that several preanalytical and analytical factors can influence the reliability and precision of the qPCR assay.
View Article and Find Full Text PDFAgeing Res Rev
September 2025
Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy; Department of Medicine and Surgery, LUM University, Casamassima, Italy. Electronic address:
Nuclear insertions of mitochondrial DNA (mtDNA) segments (NUMTs) represent an evolutionarily conserved phenomenon originating from the ancient endosymbiotic relationship between mitochondria and host cells. These insertions predominantly localize near intergenic or regulatory regions and are often enriched in tissues with high metabolic activity. Once regarded as inert pseudogenes or genomic artifacts, NUMTs are now recognized as dynamic elements capable of modulating nuclear architecture and cellular function.
View Article and Find Full Text PDFCell Stem Cell
September 2025
Sanford Stem Cell Institute Integrated Space Stem Cell Orbital Research (ISSCOR) Center, Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address:
Human hematopoietic stem and progenitor cell (HSPC) fitness declines following exposure to stressors that reduce survival, dormancy, telomere maintenance, and self-renewal, thereby accelerating aging. While previous National Aeronautics and Space Administration (NASA) research revealed immune dysfunction in low-earth orbit (LEO), the impact of spaceflight on human HSPC aging had not been studied. To study HSPC aging, our NASA-supported Integrated Space Stem Cell Orbital Research (ISSCOR) team developed bone marrow niche nanobioreactors with lentiviral bicistronic fluorescent, ubiquitination-based cell-cycle indicator (FUCCI2BL) reporter for real-time HSPC tracking in artificial intelligence (AI)-driven CubeLabs.
View Article and Find Full Text PDFExtremely short telomeres cause bone marrow failure in telomere biology disorder (TBDs) patients. Here, we employed the recently developed 'Telomouse' with human-length telomeres resulting from a single amino acid substitution in the helicase Rtel1 (Rtel1M492K/M492K) to determine the effects of the short telomeres on the bone marrow and hematopoiesis. Under homeostatic conditions, Telomice have notably short telomeres but normal hematopoiesis.
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