Nucleases are enzymes whose function is to degrade nucleic acids such as ribonucleic acid or deoxyribonucleic acid. This is referred to as complete or partial digestion of the substrate.
What are nucleases?
Nucleases are generally responsible for the degradation of nucleic acids. In this process, the nucleic acid can be degraded from the ends of the nucleic acid molecules as well as from its middle. There are also so-called restriction nucleases, which only cut nucleic acid sequences from certain regions. Nucleases are classified according to various criteria. One criterion is the type of nucleic acid (deoxyribonucleic acid or ribonucleic acid). Another criterion concerns the secondary structure such as double strand or single strand. It is also important for the selection of criteria whether the degradation occurs from the ends or from the middle of the molecule. The next question is where the site of attack is located between the 5′ site and 3′ site of the sugar–phosphate scaffold. The role of sequence-specific and non-specific base sequence also enters into the determination of the classification criteria. According to these criteria, different classification classes result. Thus, nucleases can be classified into exonucleases, endonucleases, deoxyribonucleases, and ribonucleases.
Function, action, and tasks
The functions of nucleases are diverse. One important function is to cleave foreign DNA or RNA both in a sequence-specific and nonspecific manner. Restriction endonucleases are responsible for this task. They cleave the nucleic acids at specific sites away from its ends. In the process, either similar nucleic acid sequences are cleaved or non-specific sequences are produced. The restriction endonucleases are part of the immune system, as they degrade foreign nucleic acids. Nonspecific nucleases are often responsible for digesting nucleic acids. However, they also digest the nucleic acids of dead cells during programmed cell death, apoptosis. DNase, which is particularly abundant in the pancreas, liver, platelets and blood plasma, plays a major role in this process. The mRNA is influenced by the presence of RNases. The controlled degradation of RNA controls the regulation of gene expression. The exonucleases degrade the individual DNA or RNA molecules from the ends. Here, the nucleic acid sequence is irrelevant. The function of these enzymes is to completely degrade the nucleic acids into the corresponding nucleotides. In the process, the nucleotides either serve again as building blocks for the renewed construction of nucleic acids or they are completely degraded. In genetic engineering procedures, restriction nucleases are used as molecular cutting tools for targeted removal of unwanted nucleic acid sequences.
Formation, occurrence, properties, and optimal values
The distinction between DNases and RNases is a particularly important distinguishing criterion. DNases degrade DNA. There are both neutral and acidic DNases. The neutral DNases are produced particularly in the pancreas, liver, blood plasma and platelets. There they control the degradation of DNA in the course of apoptosis. The degradation of DNA by neutral DNase leads to the formation of nucleoside’-5 phosphates. In order not to degrade the genetic material unspecifically, neutral DNase forms a complex with the protein actin. This complex is considered to be the storage form of the nuclease. Acid DNase (DNase II) is also present in the pancreas and blood plasma, but also in urine and breast milk. With the help of acid DNase, DNA is cleaved into nucleoside’-3 phosphates. RNases show a greater diversity. In humans, about 50 different RNases are known, 9 of which are associated with rare hereditary diseases. The RNases can in turn be divided into exoribonucleases and endoribonucleases, depending on whether the RNA is degraded from the ends or cleaved within the strand. Among other functions, RNases play an important role in gene regulation by specifically limiting the lifespan of tRNA. They also assist in the production of new RNA in a precisely fitting manner. Furthermore, as a component of the immune system, they are involved in combating invading viral RNA. The most important RNases include RNase A, RNase H, RNase P, RNase R and RNase D. RNase A specifically cleaves RNA according to a pyrimidine nitrogen base such as uracil or cytosine.It is particularly present in sweat, where it breaks down viruses before they can enter the organism. For this reason, it is often referred to as an environmental nuclease. RNase H acts non-specifically on DNA-RNA heteroduplexes, degrading the RNA portion. A heteroduplex of RNA and DNA is a double strand composed of the two different types of nucleic acids. RNase removes the RNA monomers that are mistakenly incorporated into the DNA and replaces them with DNA monomers. RNase P removes the precursor in the production of tRNA. RNase R helps degrade bacterial mRNA, and RNase D is partly responsible for processing tRNA.
Diseases and disorders
Nucleases are enzymes whose absence or malfunction can lead to serious physical ailments. As mentioned earlier, nine RNases are associated with very rare hereditary diseases. For example, insufficient activity of RNase H leads to mutations, strand breaks and accumulation of DNA sequences in RNA. This results in the so-called Aicardi-Goutières syndrome, which already manifests itself in the infants in febrile episodes, vomiting and fidgetiness. In some infants, learned motor skills are lost again after a few months. Many patients die in early childhood. These symptoms are caused by inflammatory reactions mediated by immune responses to the enriched DNA segments in the RNA.
