Deoxyribonuclease (DNAse) and Its Inhibitor

Ismatul Fauziah Rambe, Zulham Yamamoto


Deoxyribonuclease (DNAse) is an enzyme that plays an important role in cell apoptosis and has the function of hydrolyzing DNA. There are two types of DNAse, namely i) DNAse I which works well at neutral pH (6.5-8.0) and requires bivalent ions such as magnesium (Mg2+) and calcium (Ca2+) for activation, and ii) DNAse II which works by good at acidic pH and does not require bivalent ions. DNAse inhibitors are required to control the activity of DNAse. Both DNAse and its inhibitors have a role in the pathogenesis of various diseases, such as in the autoimmune disease systemic lupus erythematosus. DNase inhibitors can be obtained from natural, conventional, or chemical sources.


DNA, DNAse, DNAse inhibitor, enzyme, autoimun disease

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Susman M. Genes: Definition and Structure. eLS. 2014;(Molecular Biology):19.

Alberts B, Johnson A, Lewis J. The Structure and Function of DNA - Molecular Biology of the Cell - NCBI Bookshelf [Internet]. 2002. Available from: file:///Users/elenisullivan/Downloads/The Structure and Function of DNA - Molecular Biology of the Cell - NCBI Bookshelf.html

Liu Y, Zheng Z, Gong H, Liu M, Guo S, Li G, et al. DNA preservation in silk. Biomater Sci. 2017;5(7):127992.

Nussbaum RL, McInnes RR, Willard HF, Hamosh A. Tools of Human Molecular Genetics. Thompson &amp Thompson Genetics in Medicine. 2007. 4158 p.

Singh R, Sophiarani Y. A Report on DNA Sequence Determinants in Gene Expression. Bioinformation. 2020;16(5):422.

Travers A, Muskhelishvili G. DNA structure and function. FEBS J. 2015;282(12):227995.

OBrien J, Hayder H, Zayed Y, Peng C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol (Lausanne). 2018;9(AUG):112.

Ying SY, Chang DC, Lin SL. The MicroRNA (miRNA): Overview of the RNA genes that modulate gene function. Mol Biotechnol. 2008;38(3):25768.

Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol [Internet]. 2021;22(2):96118. Available from:

Morris K V. siRNA-mediated transcriptional gene silencing: The potential mechanism and a possible role in the histone code. Cell Mol Life Sci. 2005;62(24):305766.

Panawala L. Difference Between DNA and Genes. Pediaa. 2017;(February):18.

Kolarevic A, Yancheva D, Kocic G, Smelcerovic A. Deoxyribonuclease inhibitors. Eur J Med Chem [Internet]. 2014;88:10111. Available from:

Farrera C, Fadeel B. Macrophage Clearance of Neutrophil Extracellular Traps Is a Silent Process. J Immunol. 2013;191(5):264756.

Laukov L, Kone?n B, Janovi?ov L, Vlkov B, Celec P. Deoxyribonucleases and their applications in biomedicine. Biomolecules. 2020;10(7):120.

Tamkovich SN, Cherepanova A V., Kolesnikova E V., Rykova EY, Pyshnyi D V., Vlassov V V., et al. Circulating DNA and DNase activity in human blood. Ann N Y Acad Sci. 2006;1075:1916.

Napirei M, Karsunky H, Zevnik B, Stephan H, Mannherz HG, Mry T. Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Genet. 2000;25(2):17781.

Hartmann G. Nucleic Acid Immunity [Internet]. 1st ed. Vol. 133, Advances in Immunology. Elsevier Inc.; 2017. 121169 p. Available from:

Ramirez AV, Abendroth J, Mejia AA, Phan IQ, Lorimer DD, Edwards TE, et al. Structure of acid deoxyribonuclease. Nucleic Acids Res. 2017;45(10):621727.

Zhdanov DD, Fahmi T, Wang X, Apostolov EO, Sokolov NN, Javadov S, et al. Regulation of apoptotic endonucleases by EndoG. DNA Cell Biol. 2015;34(5):31626.

Evans CJ, Aguilera RJ. DNase II: Genes, enzymes and function. Gene. 2003;322(12):115.

Nagata S. Apoptotic DNA fragmentation. Exp Cell Res. 2000;256(1):128.

Keyel PA. DNAses in Health and Disease. Dev Biol [Internet]. 2017;429(1):111. Available from:

Funakoshi A, Wakasugi H, Ibayashi H. Clinical Investigatiom Of Serum Deoxyribonuclease: II. Clinical Studies of Serum Deoxyribonuclease Activity in Pancreatic Disease. Gastroenterol Jpn. 1979;14(5):43640.

Valle FM, Balada E, Ordi-Ros J, Vilardell-Tarres M. DNase 1 and systemic lupus erythematosus. Autoimmun Rev. 2008;7(5):35963.

Patel PS, Patel BP, Rawal RM, Raval GN, Patel MM, Patel JB, et al. Evaluation of serum alkaline DNase activity in treatment monitoring of head and neck cancer patients. Tumor Biol. 2000;21(2):829.

Spandidos DA, Ramandanis G, Garas J, Kottaridis SD. Serum deoxyribonucleases in patients with breast cancer. Eur J Cancer. 1980;16(12):16159.

Sumby P, Barbian KD, Gardner DJ, Whitney AR, Welty DM, Long RD, et al. Extracellular deoxyribonuclease made by group A Streptococcus assists pathogenesis by enhancing evasion of the innate immune response. PNAS. 2005;102(5):167984.

Zagorovsky K, Chou LYT, Chan WCW. Controlling DNANanoparticle Serum Interactions. Proc Natl Acad Sci U S A. 2016;113(48):136005.

Frittitta L, Camastra S, Baratta R, Costanzo B V., DAdamo M, Graci S, et al. A soluble PC-1 circulates in human plasma: Relationship with insulin resistance and associated abnormalities. J Clin Endocrinol Metab. 1999;84(10):36205.

Shuster AM, Gololobov G V., Kvashuk OA, Bogomolova AE, Smirnov I V., Gabibov AG. DNA hydrolyzing autoantibodies. Science (80- ). 1992;256(5057):6657.

del Prado A, Rodrguez I, Lzaro JM, Moreno-Morcillo M, de Vega M, Salas M. New insights into the coordination between the polymerization and 3?-5? exonuclease activities in ?29 DNA polymerase. Sci Rep. 2019;9(1):113.

Gveli ?. Inhibition of DNase I Enzyme with Nickel(II) Triphenylphosphine Complexes Incorporating Tridentate Schiff Base Ligands in Vitro. J Turkish Chem Soc Sect A Chem. 2018;5(3):1399406.

Jang DS, Penthala N, Apostolov, Eugene O. Wang X, Fahmi T, Crooks PA, Basnakian AG. Novel High-Throughput Deoxyribonuclease 1 Assay. J Biomol Screen. 2015;20(2):20211.

Takeshita H, Yasuda T, Nakazato E, Nakajima T, Mori S, Mogi K, et al. Use of human recombinant DNase I expressed in COS-7 cells as an immunogen to produce a specific anti-DNase I antibody. Exp Clin Immunogenet. 2001;18(4):22632.

Takeshita H, Mogi K, Yasuda T, Nakajima T, Nakashima Y, Mori S, et al. Mammalian deoxyribonucleases I are classified into three types: Pancreas, parotid, and pancreas-parotid (mixed), based on differences in their tissue concentrations. Biochem Biophys Res Commun. 2000;269(2):4814.

Ueki M, Takeshita H, Fujihara J, Ueta G, Nakajima T, Kominato Y, et al. Susceptibility of mammalian deoxyribonucleases I (DNases I) to proteolysis by proteases and its relationships to tissue distribution: Biochemical and molecular analysis of equine DNase I. Comp Biochem Physiol - B Biochem Mol Biol. 2007;148(1):93102.

Baranovskii AG, Buneva VN, Nevinsky GA. Human deoxyribonucleases. Biochem. 2004;69(6):587601.

Yasuda T, Nadano D, Iida R, Takeshita H, Lane SA, Callen DF, et al. Chromosomal assignment of the human deoxyribonuclease I gene, DNASE1 (DIML1), to band 16p13.3 using the polymerase chain reaction. Cytogenet Genome Res. 1995;70(34):2213.

Yasuda T, Kishi K, Yanagawa Y, Yoshida A. Structure of the human deoxyribonuclease I (DNase I) gene: identification of the nucleotide substitution that generates its classical genetic polymorphism. Ann Hum Genet. 1995;59(1):115.

Jones SJ, Worrall AF, Connolly BA. Site-directed Mutagenesis of the Catalytic Residues of Bovine Pancreatic Deoxyribonuclease I. J Mol Biol. 1996;264(5):115463.

Liu MF, Wu XP, Wang XL, Yu YL, Wang WF, Chen QJ, et al. The Functions of Deoxyribonuclease II in Immunity and Development. DNA Cell Biol. 2008;27(5):2238.

Torriglia A, Perani P, Brossas JY, Chaudun E, Treton J, Courtois Y, et al. L-DNase II, a Molecule That Links Proteases and Endonucleases in Apoptosis, Derives from the Ubiquitous Serpin Leukocyte Elastase Inhibitor. Mol Cell Biol. 1998;18(6):36129.

Krieser RJ, MacLea KS, Park JP, Eastman A. The cloning, genomic structure, localization, and expression of human deoxyribonuclease II?. Gene. 2001;269(12):20516.

Shpak M, Kugelman JR, Varela-Ramirez A, Aguilera RJ. The phylogeny and evolution of deoxyribonuclease II: An enzyme essential for lysosomal DNA degradation. Mol Phylogenet Evol. 2008;47(2):84154.

Minchew CL, Didenko V V. Quick Detection of DNase II-Type Breaks in Formalin-Fixed Tissue Sections. Cycle. 2017;1897(Figure 1):1135.

Kawane K, Fukuyama H, Kondoh G, Takeda J, Ohsawa Y, Uchiyama Y, et al. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science (80- ). 2001;292(5521):15469.

Padron-Barthe L, Leprtre C, Martin E, Counis M-F, Torriglia A. Conformational Modification of Serpins Transforms Leukocyte Elastase Inhibitor into an Endonuclease Involved in Apoptosis. Mol Cell Biol. 2007;27(11):402836.

De Maria A, Bassnett S. DNase II? distribution and activity in the mouse lens. Investig Ophthalmol Vis Sci. 2007;48(12):563846.

Yasuda T, Takeshita H, Nakazato E, Nakajima T, Hosomi O, Nakashima Y, et al. Activity Measurement for Deoxyribonucleases. Methods. 1998;2746.

Vancevska A, Nikolic A. Assessment of deoxyribonuclease activity in biological samples by a fluorescence detection-based method. Lab Med. 2013;44(2):1258.

McGuire AL, Bennett SC, Lansley SM, Popowicz ND, Della Vergiliana JFV, Wong D, et al. Preclinical assessment of adjunctive tPA and DNase for peritoneal dialysis associated peritonitis. PLoS One. 2015;10(3):115.

Barra GB, Santa Rita TH, Vasques J de A, Chianca CF, Nery LFA, Costa SSS. EDTA-mediated inhibition of DNases protects circulating cell-free DNA from ex vivo degradation in blood samples. Clin Biochem [Internet]. 2015;48(15):97681. Available from:

Yagi N, Satonaka K, Horio M, Shimogaki H, Tokuda Y, Maeda S. The role of DNase and EDTA on DNA degradation in formaldehyde fixed tissues. Biotech Histochem. 1996;71(3):1239.

Rosenberg NL. ATP as an alternative inhibitor of bacterial and endogenous nucleases and its effect on native chromatin compaction. Mol Cell Biochem. 1987;76(2):11321.

Macanovic M, Lachmann PJ. Measurement of deoxyribonuclease I (DNase) in the serum and urine of systemic lupus erythematosus (SLE)-prone NZB/NZW mice by a new radial enzyme diffusion assay. Clin Exp Immunol. 1997;108(2):2206.

Lahiri SS, Singh R. A simple method of inhibition of DNase activity in pancreatic RNase preparations. Vol. 59, Current Science. 1990. p. 12546.

Wiame I, Remy S, Swennen R, Sagi L. Irreversible heat inactivation of DNase I without RNA degradation. Biotechniques. 2000;29(2):2526.

Santos JA, Luz GA, Oliveira KP, Oliveira LF, Andrade Jnior AS, Valente SES, et al. DNase concentration assay to obtain DNA-free RNA from sugarcane leaves. Genet Mol Res. 2016;15(4).

Sperinde JJ, Choi SJ, Szoka FC. Phage display selection of a peptide DNase II inhibitor that enhances gene delivery. J Gene Med. 2001;3(2):1018.

Yamada Y, Fujii T, Ishijima R, Tachibana H, Yokoue N, Takasawa R, et al. DR396, an apoptotic DNase ? inhibitor, attenuates high mobility group box 1 release from apoptotic cells. Bioorganic Med Chem [Internet]. 2011;19(1):16871. Available from:




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