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Super killer (SKI) complex is a well-known cytoplasmic 3'-5' mRNA decay complex that functions with the exosome to degrade excessive and aberrant mRNAs, is implicated with the extraction of mRNA at stalled ribosomes, tackling aberrant translation. Here, we show that SKIV2L and TTC37 of the hSKI complex are present within the nucleus, localize on chromatin and at some telomeres during the G2 cell cycle phase. In cells, SKIV2L prevents telomere replication stress, independently of its helicase domain, and increases the stability of telomere DNA-RNA hybrids in G2. We further demonstrate that purified hSKI complex binds telomeric DNA and RNA substrates and SKIV2L association with telomeres is dependent on DNA-RNA hybrids. Taken together, our results provide a nuclear function for SKIV2L of the hSKI complex in overcoming replication stress at telomeres mediated by its recruitment to DNA-RNA hybrid structures in G2 and thus maintaining telomere stability.
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http://dx.doi.org/10.1016/j.isci.2024.111096 | DOI Listing |
Cell Discov
September 2025
National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, Hubei, China.
In the evolutionary arms race between bacteria and viruses, retrons have emerged as distinctive antiphage defense systems. Here, we elucidate the structure and function of Retron-Eco2, which comprises a non-coding RNA (ncRNA) that encodes multicopy single-stranded DNA (msDNA, a DNA‒RNA hybrid) and a fusion protein containing a reverse transcriptase (RT) domain and a topoisomerase-primase-like (Toprim) effector domain. The Eco2 msDNA and RT-Toprim fusion protein form a 1:1 stoichiometric nucleoprotein complex that further assembles into a trimer (msDNA:RT-Toprim ratio of 3:3) with a distinctive triangular configuration.
View Article and Find Full Text PDFPhys Chem Chem Phys
September 2025
Center S3, CNR Institute of Nanoscience, via Campi 213/A, 41125 Modena, Italy.
Infrared spectroscopy is widely used to probe the structural organization of biologically relevant molecules, including peptides, proteins, and nucleic acids. The latter show significant structural diversity, and specific infrared bands provide insights into their conformational ensembles. Among DNA/RNA infrared bands, the CO stretching modes are especially useful, as they are sensitive to the distinct structural arrangements within nucleic acids.
View Article and Find Full Text PDFNanoscale
August 2025
Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France.
DNA-functionalized nanoparticles (NPs), called spherical nucleic acids (SNAs), have attracted considerable attention due to their unique properties and numerous applications. In particular, DNA-functionalized dye-loaded polymeric NPs (DNA-NPs), owing to their exceptional fluorescence brightness, have emerged as powerful nanomaterials for the ultrasensitive detection and imaging of nucleic acids. Herein, we addressed a fundamental question unexplored for polymeric DNA-NPs: how does the dense packing of oligonucleotides on the particle surface impact their capacity to specifically hybridize with complementary sequences? Using Förster resonance energy transfer (FRET) between DNA-NPs and labelled complementary strands, we found that the DNA on the surface of the NPs exhibits dramatic enhancement in duplex stability compared to free DNA duplexes (>20 °C).
View Article and Find Full Text PDFNucleic Acids Res
August 2025
Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Trojdena 4, Warsaw 02-109, Poland.
R-loops are nucleic acid structures composed of an RNA/DNA hybrid and a displaced single-stranded DNA that form during transcription. Their defective processing has been implicated in genome instability, which is associated with severe human diseases. Despite their biological significance, the mechanisms regulating R-loops remain incompletely understood, underscoring the need for improved tools to accurately map R-loops across the genome.
View Article and Find Full Text PDFJ Transl Med
August 2025
Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, People's Republic of China.
R-loop is a special DNA-RNA hybrid genomic structure. Since its identification, the molecular mechanisms of physiological processes such as class switch recombination have been revealed, uncontrolled regulation of which has become the underlying cause of many diseases. With the development of molecular biology techniques, R-loops found at different sites and formed via different mechanisms have been discovered.
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