Deoxyribonuclease is an enzyme that cleaves DNA and is also known as DNase. It is involved in the repair of damaged DNA, and is used clinically to treat cystic fibrosis. Bacterial deoxyribonucleases have been instrumental in establishing the techniques of genetic engineering.
There are various types of deoxyribonucleases, but they all have in common the cleavage of the phosphate bond of the bases that make up the DNA backbone. Exodeoxyribonucleases cleave DNA from the end of the chain of bases that make up a DNA molecule and travel inwards. These act on single-stranded DNA and are non-specific. Endonucleases cleave DNA within the chain. Some are very specific and require certain base sequences to act, while others do not discriminate and will cleave anywhere.
Humans produce two different types of deoxyribonuclease that are endonucleases. Deoxyribonuclease I and II differ in the products they produce and the pH at which they are active. Deoxyribonuclease II may be involved in programmed cell death, or the targeted death of cells.
The primary function of deoxyribonuclease in higher organisms, and a major function in all organisms, is in DNA repair. DNA can be damaged through a variety of mechanisms, and there is a repair pathway that involves excising the damaged DNA. An endonuclease recognizes the damaged DNA and cleaves it on either side where the damage has been done. Then an exodeoxyribonuclease removes the damaged DNA, leaving a gap. This gap is filled in by a DNA polymerase, or an enzyme that synthesizes DNA.
DNA repair also takes place as the DNA is made. If an error is detected, it will be fixed by a DNA polymerase that has exodeoxyribonuclase activity. It will cleave the incorrect base, so that the correct one can be inserted.
Human deoxyribonuclease has clinical applications. People that suffer from cystic fibrosis have white blood cells full of DNA accumulating in their mucus. Human recombinant deoxyribonuclease I is given in an aerosol form to such patients. It degrades the DNA and helps clear the mucus from the lungs. This treatment was approved in 1993 in the United States.
Deoxyribonucleases are of great utility as restriction enzymes. Some of the endonucleases cleave only at specific sets of bases. They can be used to break down DNA, producing fragments that can be separated by gel electrophoresis to produce specific patterns. In humans, if regions of DNA are used that are highly variable, the digestions can give patterns that are unique, like fingerprints. Such fingerprinting has been highly useful for paternity testing and forensic work.
Bacterial deoxyribonucleases break down the DNA of invading organisms, such as viruses. They tend to target very specific targets on the DNA. The discovery of these restriction enzymes helped start the biotechnology revolution. The specificity of the cleavage has enabled researchers to use these enzymes in genetic engineering experiments.
