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Recombinant Human Deoxyribonuclease I

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Pharmaceutical Biotechnology

Abstract

Human deoxyribonuclease I (DNase I) is an endonuclease that catalyzes the hydrolysis of extracellular DNA and is just one of the numerous types of nucleases found in nature (Horton 2008; Yang 2011). It is the most extensively studied member of a recently discovered family of DNase I-like nucleases (Lazarus 2002; Baranovskii et al. 2004; Shiokawa and Tanuma 2001); the homologous bovine DNase I has received even greater attention historically (Laskowski 1971; Moore 1981; Chen and Liao 2006). Mammalian DNases have been broadly divided into several families initially based upon their products, pH optima, and divalent metal ion requirements. These include the neutral DNase I family (EC 3.1.21.1), the acidic DNase II family (EC 3.1.22.1), as well as apoptotic nucleases such as DFF40/CAD and endonuclease G (Lazarus 2002; Evans and Aguilera 2003; Widlak and Garrard 2005). The human DNase I gene resides on chromosome 16p13.3 and contains 10 exons and 9 introns, which span 15 kb of genomic DNA (Kominato et al. 2006). DNase I is synthesized as a precursor and contains a 22-residue signal sequence that is cleaved upon secretion, resulting in the 260-residue mature enzyme. It is secreted by the pancreas and parotid glands, consistent with its proposed primary role of digesting nucleic acids in the gastrointestinal tract. However, it is also present in blood and urine as well as other tissues, suggesting additional functions.

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Authors and Affiliations

  1. Department of Early Discovery Biochemistry, Genentech Inc., 1 DNA Way, MS27, South San Francisco, CA, 94080, USA

    Robert A. Lazarus Ph.D.

  2. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA

    Jeffrey S. Wagener M.D.

Authors
  1. Robert A. Lazarus Ph.D.
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  2. Jeffrey S. Wagener M.D.
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Correspondence to Robert A. Lazarus Ph.D. .

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Editors and Affiliations

  1. Department of Pharmaceutical Sciences, Utrecht University, Utrecht, Utrecht, The Netherlands

    Daan J. A. Crommelin

  2. Department of Pharmaceutical Sciences and Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada

    Robert D. Sindelar

  3. Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, College of Pharmacy, Memphis, Tennessee, USA

    Bernd Meibohm

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Lazarus, R.A., Wagener, J.S. (2013). Recombinant Human Deoxyribonuclease I. In: Crommelin, D., Sindelar, R., Meibohm, B. (eds) Pharmaceutical Biotechnology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6486-0_16

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