DNA articles within Nature Communications

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  • Article
    | Open Access

    The DNA helicase ASCC3 is the largest subunit of the activating signal co-integrator complex (ASCC), and its DNA unwinding activity is required for the AlkBH3/ASCC-dependent DNA de-alkylation repair pathway. Here, the authors identify a minimal stable complex of the two ASCC subunits ASCC2 and ASCC3, determine the complex crystal structure and further show that cancer-related mutations at the interface between both proteins reduce ASCC2–ASCC3 affinity.

    • Junqiao Jia
    • , Eva Absmeier
    •  & Markus C. Wahl
  • Article
    | Open Access

    Polymerase μ (Polμ) participates in the repair of DNA double-strand breaks (DSBs) via the nonhomologous end-joining (NHEJ) pathway. Here, the authors determine the crystal structure of a pre-catalytic ternary complex of human Polμ with a bound DSB substrate and they obtain further mechanistic insights by allowing the insertion reaction to proceed in crystallo, which enabled them to determine a Polμ structure with incomplete incorporation and the structure of the post-catalytic nicked state.

    • Andrea M. Kaminski
    • , John M. Pryor
    •  & Katarzyna Bebenek
  • Article
    | Open Access

    Single molecule force measurements have shed light on dynamic biological events, but rare events escape notice owing to low throughput of the methods. Here, the authors combine an array of magnetic tweezers with lateral flow to increase throughput 100-fold, and detect rare DNA breaks induced by gyrase.

    • Rohit Agarwal
    •  & Karl E. Duderstadt
  • Article
    | Open Access

    The origin recognition complex (ORC) is essential for loading the Mcm2–7 replicative helicase onto DNA during DNA replication initiation. Here, the authors describe several cryo-electron microscopy structures of Drosophila ORC bound to DNA and its cofactor Cdc6 and also report an in vitro reconstitution system for Drosophila Mcm2–7 loading, revealing unexpected features of ORC’s DNA binding and remodeling mechanism during Mcm2–7 loading.

    • Jan Marten Schmidt
    •  & Franziska Bleichert
  • Article
    | Open Access

    Cas12a-linked base editors can broaden the targeting scope of programmable cytidine deaminases. Here the authors assess their target specificity in an in vitro genome-wide assay.

    • Daesik Kim
    • , Kayeong Lim
    •  & Jin-Soo Kim
  • Article
    | Open Access

    G4 structure-interacting proteins have been linked to DNA repair processes. Here the authors reveal that in yeast, Zuo1 associates with G4 structures and plays a role in repair pathway choice by promoting nucleotide excision repair and ultimately contributing to maintenance of genome stability.

    • Alessio De Magis
    • , Silvia Götz
    •  & Katrin Paeschke
  • Article
    | Open Access

    During eukaryotic chromosome replication cells utilize ring-shaped CMG helicase that separates the two strands of the DNA double helix. Here the authors reveal that CMG helicase activity is inhibited by duplex DNA engagement at the fork, which is relieved by binding of RPA to the lagging-strand template.

    • Hazal B. Kose
    • , Sherry Xie
    •  & Hasan Yardimci
  • Article
    | Open Access

    Nucleic acid-based materials are usually only compatible with aqueous solutions. Here, the authors show a structural nucleic acid nanotechnology using gamma-modified peptide nucleic acids that enables formation of solvent-compatible, self-assembling nanostructures defined by Watson-Crick base pairing.

    • Sriram Kumar
    • , Alexander Pearse
    •  & Rebecca E. Taylor
  • Article
    | Open Access

    Some transcription factors have been proposed to functionally interact with RNA to facilitate proper regulation of gene expression. Here the authors demonstrate that human Sox2 interact directly and with high affinity to RNAs through its HMG DNA-binding domain.

    • Zachariah E. Holmes
    • , Desmond J. Hamilton
    •  & Robert T. Batey
  • Article
    | Open Access

    Pol δ bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand in eukaryotes and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. Here, the authors present a Cryo-EM structure of the human 4-subunit Pol δ bound to DNA and PCNA in a replicating state with an incoming nucleotide in the active site.

    • Claudia Lancey
    • , Muhammad Tehseen
    •  & Alfredo De Biasio
  • Article
    | Open Access

    The DNA duplex is known to be split apart in a steric exclusion manner during replication, but the specific mechanism has remained unclear. Here the authors present a cryo-EM structure of a eukaryotic replicative CMG helicase on forked DNA, revealing the mechanism of DNA unwinding.

    • Zuanning Yuan
    • , Roxana Georgescu
    •  & Michael E. O’Donnell
  • Article
    | Open Access

    To carry out their function, transcription factors must efficiently recognize specific DNA sequence targets, a complex problem in the context of eukaryotic chromatin. Here the authors use single-molecule biophysical experiments, statistical mechanical theory and bioinformatics analyses to conclude that interactions with non-target sequences near promoters serve to increase overall affinity and targeting efficiency.

    • Milagros Castellanos
    • , Nivin Mothi
    •  & Victor Muñoz
  • Article
    | Open Access

    Antiviral defence type III CRISPR systems produce cyclic oligoadenylates (cOA) as second messengers that activate downstream effectors. Here the authors present the crystal structure of the type III CRISPR defence DNA nuclease Can1 in complex with cyclic tetra-adenylate (cA4) and show that Can1 nicks supercoiled DNA.

    • Stephen A. McMahon
    • , Wenlong Zhu
    •  & Tracey M. Gloster
  • Article
    | Open Access

    Z-DNA-forming CG repeats are mutagenic in mammalian cells but the mechanism has remained unknown so far. Here, the authors show that the nucleotide excision repair complex Rad10-Rad1 (ERCC1-XPF) and the mismatch repair complex Msh2-Msh3 (MSH2-MSH3) are required for Z-DNA-induced genetic instability in yeast and human cells.

    • Jennifer A. McKinney
    • , Guliang Wang
    •  & Karen M. Vasquez
  • Article
    | Open Access

    Torsional stress is generated during DNA replication and transcription, however, the propagation of twist in condensed chromatin is poorly understood. Here the authors measure how force and torque impact chromatin fibers and find that the fibers fold into a left-handed superhelix that can be stabilized by positive torsion, suggesting that chromatin fibers stabilize nucleosomes under torsional stress.

    • Artur Kaczmarczyk
    • , He Meng
    •  & Nynke H. Dekker
  • Article
    | Open Access

    DNA composite materials have potential for biomedical sciences; however, control over the materials can be an issue. Here, the authors report on a carbon-nanotube reinforced DNA-silica gel with controllable mechanical properties to steer the attachment, proliferation, migration and release of cells.

    • Yong Hu
    • , Carmen M. Domínguez
    •  & Christof M. Niemeyer
  • Article
    | Open Access

    The mechanics of MMR strand specific excision that begins at a distant ssDNA break are not yet clear. Here the authors have used multiple single molecule imaging techniques to visualize the behavior of MMR components on mismatched DNA substrates and reveal an exonuclease-independent mechanism for E.coli MMR.

    • Jiaquan Liu
    • , Ryanggeun Lee
    •  & Richard Fishel
  • Article
    | Open Access

    Poly(ADP-ribose) polymerase-1 (PARP-1) facilitates local chromatin relaxation and the recruitment of DNA repair factors at double strand breaks site (DSBs). Here the authors reveal that PARP-1 acts as a critical regulator of DNA end resection of DSBs.

    • Marie-Christine Caron
    • , Ajit K. Sharma
    •  & Jean-Yves Masson
  • Article
    | Open Access

    The ability to encapsulate living cells could lead to many applications. Here, the authors present a flexible method to graft DNA polymers onto bacteria, yeast and mammalian cells, polymerize them into DNA cocoons and use these to manipulate and select cells based on the encoded polymer sequences on DNA cocoons.

    • Tao Gao
    • , Tianshu Chen
    •  & Genxi Li
  • Article
    | Open Access

    The type II nuclear receptors (NRs) and the retinoid X receptor (RXR) form heterodimeric transcription factors to regulate development, metabolism, and inflammation. Here the authors employ protein-binding microarrays to comprehensively analyze the DNA binding of 12 NR:RXRα heterodimers, and report promiscuous NR-DNA binding.

    • Ashley Penvose
    • , Jessica L. Keenan
    •  & Trevor Siggers
  • Article
    | Open Access

    Replication-Factor-C (RFC) and RFC-like complexes (RLCs) mediate chromatin engagement of the proliferating cell nuclear antigen (PCNA). Here authors use biochemical and single molecule measurements to show that ATAD5-RLC has the most potent PCNA unloading activity and forms structurally distinct intermediates compared to RFC-PCNA.

    • Mi-Sun Kang
    • , Eunjin Ryu
    •  & Kyungjae Myung
  • Article
    | Open Access

    CENP-A histone variants replace histones H3 at centromeres. Here the authors use a single-chain antibody fragment (scFv) to stabilize human CENP-A nucleosome containing a native α-satellite DNA and solved its structure by cryo-EM to 2.6 Å resolution, providing insight into the structure and function of the CENP-A nucleosome.

    • Bing-Rui Zhou
    • , K. N. Sathish Yadav
    •  & Ping Zhang
  • Article
    | Open Access

    Chromatin remodelling enzymes (remodellers) regulate DNA accessibility of eukaryotic genomes, which rely in large part on an ability to reposition nucleosomes. Here the authors use three-colour single-molecule FRET to simultaneously monitor remodeller-induced DNA movements on both sides of the nucleosome in real-time.

    • Anton Sabantsev
    • , Robert F. Levendosky
    •  & Sebastian Deindl
  • Article
    | Open Access

    D-lactic acidosis typically occurs in the context of short bowel syndrome; excess D-lactate is produced by intestinal bacteria. Here, the authors identify two point mutations in the human lactate dehydrogenase D (LDHD) gene that cause enzymatic loss of function and are associated with elevated plasma D-lactate.

    • Glen R. Monroe
    • , Albertien M. van Eerde
    •  & Judith J. Jans
  • Article
    | Open Access

    Large-scale deletions of mitochondrial DNA (mtDNA) are associated with different human mitochondrial diseases and normal human ageing. Here the authors present a model for mtDNA formation based on generation sequencing analysis of patients samples and in vitro reconstituted mtDNA deletion using purified proteins.

    • Örjan Persson
    • , Yazh Muthukumar
    •  & Maria Falkenberg
  • Article
    | Open Access

    Cryo-electron microscopy can determine the structure but not the nanomechanics of biological matter. Here the authors combine force spectroscopy in cryogenic conditions with computer simulations to characterize the properties of DNA simultaneously down to the sub-nm level.

    • Rémy Pawlak
    • , J. G. Vilhena
    •  & Ernst Meyer
  • Article
    | Open Access

    Somatic alterations in the exonuclease domain of DNA polymerase ɛ have been linked to the development of highly mutated cancers. Here, the authors report that a major consequence of the most common cancer-associated Polɛ variant is a dramatically increased DNA polymerase activity.

    • Xuanxuan Xing
    • , Daniel P. Kane
    •  & Polina V. Shcherbakova
  • Article
    | Open Access

    The maintenance polyamines homeostasis is important for cell growth, and several cancers harbor elevated levels of polyamines that may contribute to sustained proliferative potential. Here the authors demonstrate that polyamines participate in DNA double-strand break repair through the stimulation of RAD51-mediated homologous DNA pairing and strand exchange.

    • Chih-Ying Lee
    • , Guan-Chin Su
    •  & Peter Chi
  • Article
    | Open Access

    Microscopic transition mechanisms impact many biophysical systems. In this work, the authors explore transition path times between thermodynamic states experimentally, and show symmetry breaking in the transition times under an external force that drives the system out of equilibrium.

    • J. Gladrow
    • , M. Ribezzi-Crivellari
    •  & U. F. Keyser
  • Article
    | Open Access

    Packaging of viral DNA depends on strong molecular motors that are powered by ATP hydrolysis. Here, the authors develop a single-molecule assay to monitor how nucleotide binding regulates motor-DNA interactions and reveal a generic mechanism that prevents exit of the whole DNA from the viral capsid during packaging.

    • Mariam Ordyan
    • , Istiaq Alam
    •  & Douglas E. Smith
  • Article
    | Open Access

    The meiotic telomere complex (MAJIN, TERB1, TERB2) tethers telomere ends to the nuclear envelope. Here the authors present the crystal structure of human MAJIN-TERB2 and combine biophysical approaches and structured illumination microscopy analysis of mouse meiotic chromosomes to characterize the molecular architecture of the wider MAJIN-TERB2-TERB1 complex and its interactions with TRF1.

    • James M. Dunce
    • , Amy E. Milburn
    •  & Owen R. Davies
  • Article
    | Open Access

    DNA phosphorothioation (PT-DNA) is a DNA backbone sulfur modification that is recognized by the type-IV restriction endonuclease ScoMcrA. Here the authors provide insights into sulfur recognition by solving the crystal structure of the PT-DNA bound sulfur-binding domain (SBD) from ScoMcrA and they further show that SBD homologs are widely spread among prokaryotes.

    • Guang Liu
    • , Wencheng Fu
    •  & Xinyi He
  • Article
    | Open Access

    PWWP2A is a chromatin-binding transcriptional regulator that mediates mitosis-progression. Here, the authors provide evidence that PWWP2A directly interacts with H2A.Z nucleosomes, DNA and H3K36me3, binds to an MTA1-specific subcomplex of the NuRD complex (M1HR) and promotes changes to histone acetylation.

    • Stephanie Link
    • , Ramona M. M. Spitzer
    •  & Sandra B. Hake
  • Article
    | Open Access

    Incorporation of mismatched nucleotides during DNA replication or repair can lead to mutagenesis. Here the authors reveal that DNA ligase can ligate NHEJ intermediates following incorporation of 8-oxodGTP or dGTP opposite T by DNA Polymerase mu (Pol mu) in vitro, which suggests that Pol mu could cause promutagenic mismatches during DSB repair.

    • Melike Çağlayan
    •  & Samuel H. Wilson