Deoxyribonuclease gamma (also termed DNase γ, deoxyribonuclease 1L3, DNASE1L3, of deoxyribonuclease I like 3) is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is

encoded In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ...

by the ''DNASE1L3'' (also termed the ''deoxyribonuclease 1L3'' or ''deoxyribonuclease 1 like 3'')

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. This gene's is located on

chromosome 3 Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans more than 201 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA ...

's " p arm", i.e., short arm, between region 1, band 4, sub-band 3 and region 2, band 1, sub-band 1 (this location's is abbreviation as 3p14.3-p21.1)

Function

DNASE1L3 belongs to the family of

deoxyribonuclease Deoxyribonuclease (DNase, for short) refers to a group of glycoprotein endonucleases which are enzymes that catalyze the hydrolytic cleavage of phosphodiester linkages in the DNA backbone, thus degrading DNA. The role of the DNase enzyme in cells ...

enzymes that are responsible for degrading

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

. Specifically, DNASE1L3 plays a key role in the breakdown of extracellular DNA, particularly DNA released from dying cells due to

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

. This function is important for maintaining cellular

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

and preventing the accumulation of DNA debris, which could otherwise trigger widespread inflammatory

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...

responses.

Clinical significance

Role in autoimmune response

Humans with inactivating mutations in both of their ''DNASE1L3'' genes have a greatly recuced ability fail to remove the extracellular DNA released by dead cell and therefore to eliminate these dead cells. This failure leads to the accumulation of DNA deposits and dead cells, which triggers

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

responses throughout the body. These inflammatory responses cause the following types of inflammatory disorders.

Systemic lupus erythematosus (SLE)

Systemic lupus erythematosus (SLE) is a disorder in which an individua's

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

loses its tolerance for and therefore mounts inflammatory attacks on certain self-

antigens In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. An ...

in various tissues. SLE most often develops in adults but in 10% to 20% of cases occurs in individuals less than 19 years old. This childhood form of SLE, termed childhood-onset SLE, juvenile-onset SLE, juvenile SLE, or pediatric SLE, is a more severe disorder than adult onset SLE in part because it more often involves

lupus nephritis Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE) and childhood-onset systemic lupus erythematosus which is a more severe form of SLE that develops in children up to 18 years old; both are autoimmune d ...

kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...

, and inflammation in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. A small percentage of pediatric SLE cases are caused by defects in both of an individual's ''DNASE1L3'' genes. These rare cases of pediatric SLE due to defective ''DNASE1L3'' genes are classified as being one of the inborn error of immunity disorders.

Other associated disorders

In extremely rare cases, inactivating mutations in the ''DNASE1L3'' genes have also been associated with the development of pediatric

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

or the hypocomplementemic urticarial vasculitis syndrome (also known as McDuffie syndrome). Among 13 patients with this syndrome, four also had rheumatoid arthritis. Individuals with DNASE1L3-deficient rheumatoid arthritis or hypocomplementemic urticarial vasculitis syndrome may concurrently present with additional inflammation-induced conditions such as alveolar hemorrhages,

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...

uveitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...

, scleritis, inflammation of the

gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow Organ (anatomy), organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath t ...

, or arthritis/

arthralgia Arthralgia () literally means ' joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceuti ...

in multiple joints.

References

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