Image & Design: Rachael Tremlett

How DNA polymerases catalyse replication and repair with contrasting fidelity

Structural subtleties in DNA polymerase active sites dictate replication accuracy. Some enzymes operate at high fidelities, others cause mutations. Both are essential for living systems to prosper.

Latest Reviews

  • Review Article |

    DNA polymerases are responsible for DNA replication, repair and mutation. Although these processes occur through conserved mechanisms, this Review highlights how large differences in the fidelity of DNA replication arise from subtle structural differences between individual DNA polymerases. These differences enable polymerases to perform diverse functions that are important to nature as well as technology.

    • Wen-Jin Wu
    • , Wei Yang
    •  & Ming-Daw Tsai
  • Perspective |

    The unique properties of ferrocene-containing compounds make them useful for treating many diseases. The most notable drug candidates — the antimalarial ferroquine and the anticancer agent ferrocifen — have been studied for more than two decades but have not yet met clinical approval. This Review describes the design of ferrocene-containing drugs as well as the challenges faced in bringing them into clinical use.

    • Malay Patra
    •  & Gilles Gasser
  • Review Article |

    Research into naturally occurring chemically modified DNA bases has been invigorated by new chemical and enzymatic methods that, when coupled with sequencing approaches, enable us to detect and decode them. These techniques will support a better understanding of the role of chemically modified DNA bases in normal physiology and disease.

    • Eun-Ang Raiber
    • , Robyn Hardisty
    • , Pieter van Delft
    •  & Shankar Balasubramanian
  • Perspective |

    The cross-electrophile coupling approach to stereocontrolled C–C bond formation provides a complementary alternative to traditional cross-coupling methods. This Perspective provides an overview of the recent development of nickel-catalysed asymmetric cross-electrophile coupling reactions. Both stereoconvergent and stereospecific examples are considered and mechanistic details are highlighted.

    • Erika L. Lucas
    •  & Elizabeth R. Jarvo
  • Review Article |

    The active template approach to interlocked molecules uses metal ions to both pre-organize reaction components and catalyse the final covalent bond formation that captures the interlocked structure. This Review looks at the history of the method, its application in the synthesis of ever more complex interlocked molecules and future directions.

    • Mathieu Denis
    •  & Stephen M. Goldup
  • Review Article |

    Surface-enhanced Raman scattering (SERS) is a physical phenomenon first discovered in 1974. SERS has since been exploited for bioanalysis because of its high sensitivity and multiplexing capabilities. This Review describes the progress made and problems faced with respect to using in vivo SERS in humans.

    • Stacey Laing
    • , Lauren E. Jamieson
    • , Karen Faulds
    •  & Duncan Graham

News & Comment

  • Comment |

    A bioeconomy — that is, an economy in which fuels, chemicals and other products are sourced from biomass — can contribute to a sustainable and prosperous future. Realizing a bioeconomy will necessitate new methods for processing the complex structure of biomass to produce commodity chemicals. Many exciting opportunities are availing themselves to chemists brave enough to tackle this challenging problem.

    • Nichole D. Fitzgerald
  • Editorial |

    A detailed picture of how DNA is copied and modified comes from a molecular-level understanding of DNA and the enzymes that process it. Why is DNA not always copied correctly, and what happens when its bases are modified?

  • Comment |

    Controversy surrounds the perceived absence of a relationship between DNA polymerase fidelity (kinetic discrimination) and free energy changes determined from DNA melting studies (thermodynamic discrimination). Thermodynamic discrimination together with aqueous solvent effects can account for kinetic fidelities on the order of those observed experimentally.

    • John Petruska
    •  & Myron F. Goodman