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  • The EMBO Journal (1997) 16, 6548 - 6558
  • doi:10.1093/emboj/16.21.6548

The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites

Michael A. Gorman1, Solange Morera1, Dominic G. Rothwell2, Eric de La Fortelle3, Clifford D. Mol4, John A. Tainer4, Ian D. Hickson2 and Paul S. Freemont1

  1. Protein Structure Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
  2. Imperial Cancer Research Fund Laboratories, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK
  3. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
  4. Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA

Correspondence to:

Paul S. Freemont, E-mail: freemont@icrf.icnet.uk

Received 17 July 1997; Revised 26 August 1997

The structure of the major human apurinic/apyrimidinic endonuclease (HAP1) has been solved at 2.2 Å resolution. The enzyme consists of two symmetrically related domains of similar topology and has significant structural similarity to both bovine DNase I and its Escherichia coli homologue exonuclease III (EXOIII). A structural comparison of these enzymes reveals three loop regions specific to HAP1 and EXOIII. These loop regions apparently act in DNA abasic site (AP) recognition and cleavage since DNase I, which lacks these loops, correspondingly lacks AP site specificity. The HAP1 structure furthermore suggests a mechanism for AP site binding which involves the recognition of the deoxyribose moiety in an extra-helical conformation, rather than a 'flipped-out' base opposite the AP site.

  • Keywords:

    • abasic sites,
    • DNA repair,
    • endonuclease,
    • HAP1,
    • Ref-1