We present a new structure of a DNA dodecamer obtained in the presence of Ni ions. The DNA forms Ni-guanine cross-links between neighboring molecules. Our results show that an adequate dosage of Ni may help to form well-defined DNA nanostructures. We also compare our structure with other dodecamers which present unique features and also crystallize in trigonal unit cells, strongly influenced by the counterions associated with DNA. In all cases, the DNA duplexes form parallel pseudo-helical columns in the crystal, similar to DNA-protamine and native DNA fibers.
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http://dx.doi.org/10.1002/bip.23397 | DOI Listing |
Nat Commun
December 2024
Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing, China.
While circular RNAs (circRNAs) exhibit lower abundance compared to corresponding linear RNAs, they demonstrate potent biological functions. Nevertheless, challenges arise from the low concentration and distinctive structural features of circRNAs, rendering existing methods operationally intricate and less sensitive. Here, we engineer an intelligent tetrahedral DNA framework (TDF) possessing precise spatial pattern-recognition properties with exceptional sensing speed and sensitivity for circRNAs.
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December 2024
Architecture and Dynamics of Biological Macromolecules, Institut Pasteur, Université Paris Cité, CNRS UMR 3528, Paris, France.
Replication Protein A (RPA) plays a pivotal role in DNA replication by coating and protecting exposed single-stranded DNA, and acting as a molecular hub that recruits additional replication factors. We demonstrate that archaeal RPA hosts a winged-helix domain (WH) that interacts with two key actors of the replisome: the DNA primase (PriSL) and the replicative DNA polymerase (PolD). Using an integrative structural biology approach, combining nuclear magnetic resonance, X-ray crystallography and cryo-electron microscopy, we unveil how RPA interacts with PriSL and PolD through two distinct surfaces of the WH domain: an evolutionarily conserved interface and a novel binding site.
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December 2024
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Biomedical Pioneering Innovative Center (BIOPIC) and Beijing Advanced Innovation Center for Genomics (ICG), Center for Bioinformatics (CBI), Peking University, 100871, Beijing, China.
Deciphering how noncoding DNA determines gene expression is critical for decoding the functional genome. Understanding the transcription effects of noncoding genetic variants are still major unsolved problems, which is critical for downstream applications in human genetics and precision medicine. Here, we integrate regulatory-specific neural networks and tissue-specific gradient-boosting trees to build SVEN: a hybrid sequence-oriented architecture that can accurately predict tissue-specific gene expression level and quantify the tissue-specific transcriptomic impacts of structural variants across more than 350 tissues and cell lines.
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December 2024
Division of Protein & Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
The rate and pattern of mutagenesis in cancer genomes is significantly influenced by DNA accessibility and active biological processes. Here we show that efficient sites of replication initiation drive and modulate specific mutational processes in cancer. Sites of replication initiation impede nucleotide excision repair in melanoma and are off-targets for activation-induced deaminase (AICDA) activity in lymphomas.
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December 2024
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
The CRISPR-associated endonuclease Cas9 derived from prokaryotes is used as a genome editing, which targets specific genomic loci by single guide RNAs (sgRNAs). The eukaryotes, the target of genome editing, store their genome DNA in chromatin, in which the nucleosome is a basic unit. Despite previous structural analyses focusing on Cas9 cleaving free DNA, structural insights into Cas9 targeting of DNA within nucleosomes are limited, leading to uncertainties in understanding how Cas9 operates in the eukaryotic genome.
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