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Structure and function of the multifunctional DNA-repair enzyme exonuclease III

Nature volume 374, pages 381–386 (1995)Cite this article

Abstract

THE repair of DNA requires the removal of abasic sites, which are constantly generated in vivo both spontaneously1 and by enzymatic removal of uracil2, and of bases damaged by active oxygen species, alkylating agents and ionizing radiation3,4. The major apurinic/ apyrimidinic (AP) DNA-repair endonuclease in Escherichia coli is the multifunctional enzyme exonuclease III, which also exhibits 3′-repair diesterase, 3′→ 5′ exonuclease, 3′-phosphomonoesterase and ribonuclease activities5. We report here the 1.7 Å resolution crystal structure of exonuclease III which reveals a 2-fold symmetric, four-layered ap fold with similarities to both deoxyribo-nuclease I6 and RNase H7. In the ternary complex determined at 2.6 Å resolution, Mn2+ and dCMP bind to exonuclease III at one end of the αβ-sandwich, in a region dominated by positive electrostatic potential. Residues conserved among AP endonucleases from bacteria to man cluster within this active site and appear to participate in phosphate-bond cleavage at AP sites through a nucleophilic attack facilitated by a single bound metal ion.

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Author notes

  1. Che-Fu Kuo

    Present address: Department of Structural Biology, Department 46Y, Building AP9A, Abbott Laboratories, One Abbott Park Road, Abbott Park, Illinois, 60064, USA

Authors and Affiliations

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

    Clifford D. Mol, Che-Fu Kuo, Maria M. Thayer & John A. Tainer

  2. Department of Biological Sciences, Center for Biochemistry and Biophysics, State University of New York-Albany, Albany, New York, 12222, USA

    Richard P. Cunningham

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  1. Clifford D. Mol
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Mol, C., Kuo, CF., Thayer, M. et al. Structure and function of the multifunctional DNA-repair enzyme exonuclease III. Nature 374, 381–386 (1995). https://doi.org/10.1038/374381a0

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