DNA metabolism articles within Nature

  • Article
    | Open Access

    RNA targeting by the Sulfuricurvum type V single-effector nuclease SuCas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA—after recognition of an RNA target through an activating protospacer-flanking sequence, SuCas12a2 efficiently degrades ssRNA, ssDNA and dsDNA.

    • Oleg Dmytrenko
    • , Gina C. Neumann
    •  & Chase L. Beisel
  • Article
    | Open Access

    The cryogenic-electron microscopy structure of the D. thermocuniculi IsrB protein in complex with its cognate ωRNA and a target DNA shows that the RNA-dominant IsrB effector complex shares a common scaffold with the protein-dominant Cas9 effector complex.

    • Seiichi Hirano
    • , Kalli Kappel
    •  & Feng Zhang
  • Article
    | Open Access

    Cryo-electron microscopy structures of Cas9 during mismatch cleavage provide insight into the mechanisms that control off-target effects of Cas9, which will aid in the future design of high-fidelity Cas9 variants with reduced off-target cleavage.

    • Jack P. K. Bravo
    • , Mu-Sen Liu
    •  & David W. Taylor
  • Article |

    Single-molecule fluorescence resonance energy transfer and real-time confocal laser tracking with fluorescence correlation spectroscopy together characterize how individual lac repressor molecules bypass operator sites while exploring the DNA surface at microsecond timescales.

    • Emil Marklund
    • , Brad van Oosten
    •  & Sebastian Deindl
  • Letter |

    ORBIT (origami-rotor-based imaging and tracking) is used to track the DNA rotation that results from DNA unwinding by RecBCD helicase and transcription by RNAP at a single-molecule scale and millisecond time resolution.

    • Pallav Kosuri
    • , Benjamin D. Altheimer
    •  & Xiaowei Zhuang
  • Article |

    Detailed structures of yeast RNA polymerase III and its initiation complex shed light on how the transcription of essential non-coding RNAs begins and allow comparisons with other RNA polymerases.

    • Guillermo Abascal-Palacios
    • , Ewan Phillip Ramsay
    •  & Alessandro Vannini
  • Letter |

    Enzymes of the nucleotide salvage pathway are shown to have substrate selectivity that protects newly synthesized DNA from random incorporation of epigenetically modified forms of cytosine; a subset of cancer cell lines that overexpress cytidine deaminase (CDA) are sensitive to treatment with 5hmdC or 5fdC (oxidized forms of 5-methyl-cytosine), which leads to DNA damage and cell death, indicating the chemotherapeutic potential of these nucleoside variants for CDA-overexpressing cancers.

    • Melania Zauri
    • , Georgina Berridge
    •  & Skirmantas Kriaucionis
  • Article |

    It has long been a goal to reconstitute eukaryotic DNA replication; here a purified in vitro system from budding yeast containing 16 factors, themselves composed of 42 polypeptides, fulfils the staged process of origin-dependent initiation, including its regulation by kinases.

    • Joseph T. P. Yeeles
    • , Tom D. Deegan
    •  & John F. X. Diffley
  • Letter |

    Crystal structure of the RNA-guided endonuclease Cas9 bound to a guide RNA and a target DNA duplex reveals how base-specific recognition of a short motif known as PAM in the DNA target results in localized strand separation in the DNA immediately upstream of the PAM, allowing the target DNA strand to hybridize to the guide RNA.

    • Carolin Anders
    • , Ole Niewoehner
    •  & Martin Jinek
  • Letter |

    Triphosphates of hydrophobic nucleotides d5SICS and dNaM are imported into Escherichia coli by an exogenous algal nucleotide triphosphate transporter and then used by an endogenous polymerase to replicate, and faithfully maintain over many generations of growth, a plasmid containing the d5SICS–dNaM unnatural base pair.

    • Denis A. Malyshev
    • , Kirandeep Dhami
    •  & Floyd E. Romesberg
  • Letter |

    The Tet family of dioxygenase enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine, which has an effect on gene expression; here the structure of NgTet1, a Tet-like protein with the same activity as mammalian Tet1, is determined, showing that NgTet1 uses a base-flipping mechanism to access 5-methylcytosine.

    • Hideharu Hashimoto
    • , June E. Pais
    •  & Xiaodong Cheng
  • Article |

    In vitro and in vivo, the yeast Pif1 helicase is able to unwind four-stranded G-quadruplex (G4) DNA efficiently and suppress the genomic instability that occurs at such structures; these G4 maintenance activities are conserved among evolutionarily diverse Pif1 family helicases, including human PIF1, demonstrating the importance of this activity throughout evolution.

    • Katrin Paeschke
    • , Matthew L. Bochman
    •  & Virginia A. Zakian
  • Article |

    The long-awaited structure of a telomerase holoenzyme, from Tetrahymena, has been obtained by electron microscopy; affinity labelling of subunits and modelling with NMR and crystal structures of various components allowed the identification of the catalytic core and subunit interactions, and the functional role of the subunits in telomerase processivity was enabled by performing the first reconstitution of the holoenzyme in vitro.

    • Jiansen Jiang
    • , Edward J. Miracco
    •  & Juli Feigon