In 1903, Araki liquefied gels of alpha-nucleic acid with extracts of liver, spleen, and thymus tissue (Araki 1903, and Kunitz 1950). Plenge also showed similar activities in microorganisms (Plenge 1903). In 1913, De la Blanchardière developed an assay for the liquification of thymus DNA gel, and showed it was not accompanied by the destruction of DNA bases (Kunitz 1950).
Over the next few decades various authors described enzymes that cleaved nucleotides with names such as nucleinase (Levene and Medigreceanu 1911), nucleogelase (Feulgen 1923), polynucleotidase (Levene and Dillon 1932), desoxyribonucleodepolymerase (Greenstein 1943), thymonucleodepolymerase (Laskowski 1946), and desoxyribonuclease (McCarty 1946). In 1950, Kunitz first crystallized and coined today’s name, deoxyribonuclease.
In the early 1970s, Salnikow et al. found DNase I was present in four isoforms distinguishable by their sialic acid contents (Salnikow et al. 1970). Soon after, the polypeptide chain structure was elucidated (Salnikow et al. 1973b, Liao et al. 1973, and Catley 1973). The crystal structure was determined at a 2.0 Å resolution by Suck and Oefner in 1986 and later refined (Oefner and Suck 1986).
In 1990, the gene coding for Bovine pancreas DNase I (bpDNase I) was constructed from synthetic oligonucleotides, and then cloned and expressed in E. coli (Worrall and Connolly 1990). In 1992, the X-ray structure of the bpDNaseI-d(GGTATACC)2 complex was obtained at a 2.3 Å resolution (Weston et al. 1992). In 1998, the bpDNaseI gene was cloned from bp-cDNA and expressed in E. coli (Chen et al. 1998).
Today, researchers continue to investigate the residues involved in substrate binding and catalytic activity (Chen et al. 2008), novel inhibitors (Chen and Liao 2008), the specificity of DNAse I for specific DNA sequences (Heddi et al. 2010), and the conformational changes that occur in both DNAse I and DNA upon protein-DNA complexation (N’soukpoé-Kossi et al. 2008).
