ABSTRACT

Human deoxyribonuclease I (DNase I) is an endonuclease that catalyzes the hydrolysis of extracellular DNA. It is the most extensively studied member of a 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/CADand endonucleaseG (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.