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  • The EMBO Journal (2007) 26, 1363 - 1372
  • doi:10.1038/sj.emboj.7601593

Published online: 22 February 2007

AP endonuclease paralogues with distinct activities in DNA repair and bacterial pathogenesis

Elisabeth P Carpenter1,a, Anne Corbett2,a, Hellen Thomson1,a, Jolanta Adacha1, Kirsten Jensen1, Julien Bergeron1,b, Ioannis Kasampalidis1,c, Rachel Exley2, Megan Winterbotham2, Christoph Tang2, Geoff S Baldwin1 and Paul Freemont1

  1. Centre for Structural Biology, Division of Molecular Biosciences, Faculty of Natural Sciences
  2. Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK

Correspondence to:

Christoph Tang, Department of Infectious Diseases, Faculty of Medicine, Centre for Molecular Microbiology and Infection, Imperial College London, London SW7 2AZ, UK. Tel.: +44 207 594 3072; E-mail: c.tang@imperial.ac.uk

Geoff S Baldwin, Division of Molecular Biosciences, Faculty of Natural Sciences, Centre for Structural Biology, Imperial College London, London SW7 2AZ, UK. Tel.: +44 207 594 5288; E-mail: g.baldwin@imperial.ac.uk

Paul Freemont, Division of Molecular Biosciences, Faculty of Natural Sciences, Centre for Structural Biology, Imperial College London, London SW7 2AZ, UK. Tel.: +44 207 594 3086; Fax: +44 207 594 3057; E-mail: p.freemont@imperial.ac.uk

aThese authors contributed equally to this work

bPresent address: Structural Biology Group, Randall Division of Cell and Molecular Biophysics, King's College London, London

cPresent address: Department of Informatics, Aristotle University of Thessaloniki, Thesssaloniki 54124, Greece

Received 29 September 2006; Accepted 21 December 2006

Oxidative stress is a principal cause of DNA damage, and mechanisms to repair this damage are among the most highly conserved of biological processes. Oxidative stress is also used by phagocytes to attack bacterial pathogens in defence of the host. We have identified and characterised two apurinic/apyrimidinic (AP) endonuclease paralogues in the human pathogen Neisseria meningitidis. The presence of multiple versions of DNA repair enzymes in a single organism is usually thought to reflect redundancy in activities that are essential for cellular viability. We demonstrate here that these two AP endonuclease paralogues have distinct activities in DNA repair: one is a typical Neisserial AP endonuclease (NApe), whereas the other is a specialised 3'-phosphodiesterase Neisserial exonuclease (NExo). The lack of AP endonuclease activity of NExo is shown to be attributable to the presence of a histidine side chain, blocking the abasic ribose-binding site. Both enzymes are necessary for survival of N. meningitidis under oxidative stress and during bloodstream infection. The novel functional pairing of NExo and NApe is widespread among bacteria and appears to have evolved independently on several occasions.

  • Keywords:

    • DNA repair,
    • exonuclease,
    • Neisseria meningitidis,
    • repair phosphodiesterase,
    • X-ray structure