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Identification of critical active-site residues in the multifunctional human DNA repair enzyme HAP1

Nature Structural Biology volume 2, pages 561–568 (1995)Cite this article

Abstract

All organisms express dedicated repair enzymes for counteracting the cytotoxic and mutagenic potential of apurinic/apyrimidinic (AP) lesions, which would otherwise pose a serious threat to genome integrity. We present the predicted three-dimensional structure of the major human AP site-specific DNA repair endonuclease, HAP1, and show that an aspartate/histidine pair, in conjunction with a metal ion-coordinating glutamate residue, are critical for catalyzing the multiple repair activities of HAP1. We suggest that this catalytic mechanism is conserved in certain reverse transcriptases, but is distinct from the two metal ion-mediated mechanism defined for other hydrolytic nucleases.

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Authors and Affiliations

  1. Imperial Cancer Research Fund, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Gil Barzilay, Craig N. Robson, Lisa J. Walker & Ian D. Hickson

  2. Department of Molecular Biology, Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California, 92037, USA

    Clifford D. Mol & John A. Tainer

  3. Department of Biological Sciences, SUNY at Albany, New York, 12222, USA

    Richard P. Cunningham

Authors
  1. Gil Barzilay
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  2. Clifford D. Mol
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  4. Lisa J. Walker
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  5. Richard P. Cunningham
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  6. John A. Tainer
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  7. Ian D. Hickson
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Barzilay, G., Mol, C., Robson, C. et al. Identification of critical active-site residues in the multifunctional human DNA repair enzyme HAP1. Nat Struct Mol Biol 2, 561–568 (1995). https://doi.org/10.1038/nsb0795-561

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