Deoxyribonucleases and Their Applications in Biomedicine

Abstract

Extracellular DNA, also called cell-free DNA, released from dying cells or activated immune cells can be recognized by the immune system as a danger signal causing or enhancing inflammation. The cleavage of extracellular DNA is crucial for limiting the inflammatory response and maintaining homeostasis. Deoxyribonucleases (DNases) as enzymes that degrade DNA are hypothesized to play a key role in this process as a determinant of the variable concentration of extracellular DNA. DNases are divided into two families—DNase I and DNase II, according to their biochemical and biological properties as well as the tissue-specific production. Studies have shown that low DNase activity is both, a biomarker and a pathogenic factor in systemic lupus erythematosus. Interventional experiments proved that administration of exogenous DNase has beneficial effects in inflammatory diseases. Recombinant human DNase reduces mucus viscosity in lungs and is used for the treatment of patients with cystic fibrosis. This review summarizes the currently available published data about DNases, their activity as a potential biomarker and methods used for their assessment. An overview of the experiments with systemic administration of DNase is also included. Whether low-plasma DNase activity is involved in the etiopathogenesis of diseases remains unknown and needs to be elucidated.

STING Mediates Lupus via the Activation of Conventional Dendritic Cell Maturation and Plasmacytoid Dendritic Cell Differentiation

“…TREX1 degrades double-stranded DNA, whereas oxidized DNA is resistant to TREX1-mediated degradation ( Gehrke et al., 2013 ; Grieves et al., 2015 ). Also, DNASE II cleaves native dsDNA but works less effectively for denaturized DNA ( Laukova et al., 2020 ). Moreover, the mitochondrial DNA (mtDNA) releasing into the cytosol can trigger the IFN-I response and accelerates the severity of a mouse model of lupus disease ( Kim et al., 2019 ).…”

Deoxyribonuclease I Inhibitory Properties, Molecular Docking and Molecular Dynamics Simulations of 1‐(Pyrrolidin‐2‐yl)propan‐2‐one Derivatives

“…Nucleases are enzymes responsible for metabolism and maintenance of nucleic acids in human body [1] . Deoxyribonuclease I (DNase I) discovered in 1946 is the oldest member of DNase I family of endonucleases that contains three more DNase I‐like nucleolytic enzymes known as DNase1 L1, DNase1 L2, and DNase1 L3 [2,3] . DNase I activity leads to endonucleolytic cleavage of double and single‐stranded DNA molecules in the presence of Mg 2+ and Ca 2+ cations under normal pH conditions producing oligonucleotides with 5′‐phospho and 3′‐hydroxy ends [4] .…”

Microfluidic Impedance Biosensor Chips Using Sensing Layers Based on DNA-Based Self-Assembled Monolayers for Label-Free Detection of Proteins

“…EDTA complexes Ca 2+ and Mg 2+ which are required as cofactors for the DNA-degrading enzymatic reaction. Hence, this complexation would reduce the interfering effects of the DNA-degrading enzymes, while troponin detection is still possible as is the detection of other proteins [ 28 , 29 , 30 ].…”