DNASE2

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Deoxyribonuclease II (DNase II), namely deoxyribonuclease II, was first discovered in 1947 and is a non-divalent cation-dependent acid endonuclease. Located in lysosomes, nuclei and cell secretions. The cloning of DNase II genes in a variety of mammals such as cattle, pigs, mice, and humans has been carried out, and the characteristics of highly homologous genes of DNase II in animals such as C. elegans, Drosophila, and scallops have been studied.

DNase II structure characteristics

• DNase II has the following structural features:
• Signal peptide leader sequence
• Cysteine is involved in the formation of disulfide bonds amino acid residues are involved in the enzymatic hydrolysis process.

Figure 1. Structure of deoxyribonuclease II.

DNase II breaks the phosphodiester bond between nucleotides in single-stranded and double-stranded, resulting in 5'-hydroxyl end and 3'-phosphate end. DNase II cleavage DNA at different positions. DNase II enzymes of different species, such as C. elegans, Drosophila melanogaster and cattle, all have obvious cleavage sites AGAGGA.

Human DNase II gene

The members of the DNase II enzyme family of mammals are: DNase IIα, DNase IIβ (DLAD). Its analog is L-DNase II. The human DNase II genome is 19p13.2. There are 1593 bases, 5 introns, 6 exons, and 360 amino acids are encoded. The enzyme has three parts: a signal peptide (16 amino acid residues), a short propeptide (91 amino acid residues) and a long mature protein of 253 amino acids. The 5´-end has the characteristics of a housekeeping gene, which is suitable for its universal expression in human tissues. There are 4 N glycosylation sites (N-X-S/T) in the structure, which may be additional sites for mannose-6-phosphate

Main functions of DNase II family

The DNase II family has many functions. The removal of DNase II will destroy the function of phagocytes and cause severe immune deficiency and affect growth and development.

• DNase II is associated with the development of autoimmune diseases

Foreign DNA can activate the innate immune system. The accumulation of undegraded DNA stimulates the production of TNF, type I IFN and IL-6. Interferon can induce DNase II a-/- mouse embryo liver to activate the gene strongly. After mating between DNase II a-/- mice and normal mice, the interferon type 1 receptor (INF-IR) is lacking and undigested DNA accumulates, causing an acute cellular response. If the apoptotic cells are not phagocytosed, the contents of the cells will be released, possibly resulting in autoimmune diseases. Adult DNase II deficient mice died of chronic polyarthritis, similar to rheumatoid arthritis. Human DNase II polymorphism is associated with increased risk of kidney disease in patients with systemic lupus erythematosus (SLE).

• DNase II can effectively resist the absorption of foreign DNA

After apoptotic cells are swallowed, genetic information will transfer from apoptotic cells to living cells, which may lead to tumorigenesis. However, the transfer of apoptotic DNA to fibroblasts or epithelial cells can cause cell cycle arrest. DNase II degrades the DNA of phagocytosed apoptotic cells to activate p53 and p21 pathway to protect normal cells against potentially harmful DNA replication. Therefore, the activation of DNase II enzyme can prevent the replication of harmful DNA, which in turn prevents the development of malignant diseases.

DNase II phylogeny and evolution

There are still many unresolved questions about the origin, phylogeny, distribution and evolution of DNase II enzyme. Early studies proved that DNase II exists in different multicellular animals, and also exists in fungi, Trichomonas and a special single bacterial genus. Porous organisms such as paramecium, unequal flagellates such as diatoms, algae, and even green algae have DNase II homologs, while red algae, flowers, fungi and some parasitic organisms are obviously lacking. Although it exists in the genus Trichomonas, it is likely to evolve at the same time as phagocytosis, which is conducive to DNA degradation and bacterial nutrition. Many eukaryotes lack DNase II to varying degrees, which can explain the lack of phagocytosis of intracellular parasites, obligate self-supporting bacteria, and saprophytic bacteria.

Reference

1. Liao T H. The subunit structure and active site sequence of porcine spleen deoxyribonuclease. Biol. Chem. 1985,260(19):10708 –10713