1 Introduction

DNase1: Deoxyribonucleotidase 1, an endonuclease is capable of digesting single-stranded or double-stranded DNA to produce a single deoxynucleotide or a single- or double-stranded oligodeoxynucleotide. The product of DNase1 has a phosphate group at the 5' end and a hydroxyl group at the 3' end after hydrolysis of single-stranded or double-stranded DNA. DNase1’s activity is dependent on calcium ions; magnesium ions and can be activated by magnesium ions or divalent manganese ions. In the presence of magnesium ions, DNase1 can randomly cleave any position of double-stranded DNA. While in the presence of divalent manganese ions, DNase 1 can cleave DNA double strands at the same site to form blunt ends, or 1-2 nucleotides protruding sticky ends.

2 Structure

The DNase1 gene is located on chromosome 16P13.3; the relative molecular weight is 32kDa including 9 exons and 8 introns. The DNase1 has been found to have alleles: DNase1L1; DNase1L2; DNase1L3; DNase1L4; DNase1L5; DNase1L6, which differs in the nucleotide of a coding region. Human Dnase1L1; L2; L3 have been identified and cloned, and their expression is specific. DNase1L1 is mainly expressed in the heart and skeletal muscle. DNase1L2 is mainly expressed in brain tissue, and DNase1L3 is mainly expressed in liver, kidney, thymus and spleen tissues.

The encoding of DNase1L3 begins with the second exon. In 1994, humans first isolated the DNase1 allele DNase1L3 from the nucleus of the two activated regions of rat immune cells (DNaseα; DNaseβ), which is closely related to humans. The molecular weight of DNase1L3 is 32KD. Under the environment of pH 7 with the activation of calcium ions; magnesium ions and the inhibition of zinc ions can hydrolyze DNA double strands to the 5' phosphate end and the 3' light base end. The gene of DNase1L3 was found to be expressed in the spleen, liver, thymus, lymph nodes, bone marrow, small intestine and kidney by in situ hybridization. Current studies have also shown that DNase1L3 is also involved in cell apoptosis and necrosis.

3 Role in disease

Tumor

DNase1L3 is a clonal allele of DNase1 and is closely related to humans. At present, the study on the relationship between Dnase1 and tumor mainly examined the concentration of DNase1 in serum, found that the activity of DNase1 in serum of breast cancer patients is significantly increased, but the activity of DNase1 in serum of patients with chronic pancreatitis and gastric cancer is significantly reduced. Shklyaeva et al injected a small amount of Dnase1 into C57B 1/6J mice, and the metastatic area of primary lung cancer was reduced by 2-8 times, which indicated that DNase1 inhibited tumor metastasis elsewhere.

DNase1L3 can degrade DNA into small molecule fragments in the presence of calcium and magnesium ions to promote cell apoptosis and necrosis. The expression of DNase1L3 in normal tissues is higher than that in cancer tissues, which may promote tumors. Apoptosis is involved.

Systemic lupus erythematosus

Researchers at the Languere Medical Center at New York University found that DNase1L3 normally digests the DNA in the micro-particles released from cell breakage to prevent the production of lupus. If DNase1L3 is not blocked from DNA accumulation, DNA accumulation triggers the production of antibodies by immune cells. Such antibodies, when combined with DNA to form a complex, enter the arterial wall and tissue, leading to the appearance of inflammation. The investigators confirmed that patients who lack the DNase1L3 gene or the DNase1L3 gene do not function contain large amounts of circulating DNA and produce antibodies against it, and such antibodies are also present in most lupus patients. This provides a new therapeutic approach for the development of DNase1L3 as a drug.

4 Usage

 Preparing a DNA-free RNA sample;
 Removal of possible DNA contamination such as genomic DNA from RNA samples prior to RT-PCR;
 RNA template after RNA transcription catalyzed by RNA polymerases such as T7, T3, and SP6 in vitro;
 DNase1 foot printing studies DNA-protein interactions;
 Nick translation;
 Generating a library of random fragments of DNA;
 Partially cut genomic DNA was used as a positive control in the apoptotic TUNEL assay.

Author's Bio: 

DNASE1L3 has several biochemical functions, for example, DNA binding, calcium ion binding, deoxyribonuclease activity. Some of the functions are cooperated with other proteins, some of the functions could acted by DNASE1L3 itself. Creative Biomart selected most functions DNASE1L3 had, and list some proteins which have the same functions with DNASE1L3. You can find most of the proteins on our site.