Molecular basis for DNA strand displacement by NHEJ repair polymerases

Edward J. Bartlett, Nigel Brissett, Przemyslaw Plocinski, Tom Carlberg, Aidan J. Doherty

    Research output: Contribution to journalArticlepeer-review


    The non-homologous end-joining (NHEJ) pathway repairs DNA double-strand breaks (DSBs) in all domains of life. Archaea and bacteria utilize a conserved set of multifunctional proteins in a pathway termed Archaeo-Prokaryotic (AP) NHEJ that facilitates DSB repair. Archaeal NHEJ polymerases (Pol) are capable of strand displacement synthesis, whilst filling DNA gaps or partially annealed DNA ends, which can give rise to unligatable intermediates. However, an associated NHEJ phosphoesterase (PE) resects these products to ensure that efficient ligation occurs. Here, we describe the crystal structures of these archaeal (Methanocella paludicola) NHEJ nuclease and polymerase enzymes, demonstrating their strict structural conservation with their bacterial NHEJ counterparts. Structural analysis, in conjunction with biochemical studies, has uncovered the molecular basis for DNA strand displacement synthesis in AP-NHEJ, revealing the mechanisms that enable Pol and PE to displace annealed bases to facilitate their respective roles in DSB repair.
    Original languageEnglish
    Pages (from-to)2173–2186
    JournalNucleic Acids Research
    Issue number5
    Publication statusPublished - 23 Sept 2015

    Bibliographical note

    © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.


    Dive into the research topics of 'Molecular basis for DNA strand displacement by NHEJ repair polymerases'. Together they form a unique fingerprint.

    Cite this