Human Deoxyribonucleases

Abstract

Although mammalian deoxyribonucleases were discovered more than 60 years ago, interest in these enzymes is not weakening. During the last decade, intensive studies of human DNases culminated in discovery of several novel enzymes exhibiting DNase activity. These include an unusual DNase, lactoferrin. For some enzymes, their three-dimensional structure and molecular mechanisms underlying their functioning have been elucidated. In patients with some autoimmune and viral diseases, catalytic antibodies also contribute to alternative pathways of DNA hydrolysis. Some enzymes exhibiting DNase activity play an important role in pathogenesis of various diseases and also in programmed cell death (apoptosis). This review highlights recent achievement in human deoxyribonuclease research. It also considers mechanisms of DNA hydrolysis. The review also summarizes modern data on the biological role of these enzymes in functioning of the human organism, realization of its protective mechanisms, and possible applications of DNases in medicine.

Diversity of DNA‐hydrolyzing antibodies from the sera of autoimmune‐prone MRL/MpJ‐lpr mice

“…These values of K m show that the affinity of catalytic mouse IgGs for DNA is about 3-5 orders of magnitude higher in comparison with all known human DNases (46-58 mM) (Baranovskii et al, 2004). These values are comparable with the affinity characterizing strong binding of Abs with antigens including interaction of plasmid scDNA with IgGs from SLE patients (K m ¼ 43 nM) (Gololobov et al, 1995) and DNase IgGs from multiple sclerosis patients (K d ¼ 0.34 nM) (Baranovskii et al, 2001).…”

Engineering a waste management enzyme to overcome cancer resistance to apoptosis: adding DNase1 to the anti-cancer toolbox

“…It is expected to be highly cytotoxic in mammalian cells as it can effectively digest both single-and double-stranded DNA, although it digests double-stranded DNA more than 100 times faster than single-stranded DNA. [10][11][12] Thus, a small amount can induce cell death. 13 Second, as a waste-management enzyme, DNase1 has no access to the nucleus under normal physiological conditions, thus, it is conceivable that DNase1 would encounter fewer nuclear inhibitors than cell-autonomous nucleases.…”

Natural Catalytic Antibodies in Norm and in HIV-Infected Patients

“…7A demonstrates three pH dependencies of different types which were revealed for catalytic pIgGs from the sera of 3 different patients. In contrast to all human DNases having one pronounced pH optimum in hydrolysis of DNA (Baranovskii et al, 2004), catalytic Abs usually show high DNase activity at a wide range of pH values between 5.5-9.0. Nevertheless, as one can see from Fig.…”