Endonucleases are enzymes that degrade DNA and RNA without completely cleaving them. The group of endonucleases includes several enzymes, each of which is substrate- and action-specific.
What is an endonuclease?
Endonucleases are various enzymes that are not unique to humans but are found in all living things. They belong to the superordinate group of nucleases. Endonucleases degrade DNA or RNA without completely cleaving it. DNA or deoxyribonucleic acid is a complex structure of sugar molecules (deoxyribose) and nucleic acids. To process DNA, endonucleases break the phosphodiester bond between the individual building blocks. The phosphodiester bond holds the DNA and RNA together at the backbone. The nucleotides of DNA and RNA have a phosphoric acid residue. It is located on the sugar, the backbone of which forms a ring. This ring has five carbon atoms; among others, an OH group, i.e. a compound of an oxygen and a hydrogen atom, is located at carbon atom C5. The carbon atom C5 and the OH group form an ester of phosphoric acid. This phosphoric acid residue obtains a second ester bond, which consists of the carbon atom C3 and the corresponding OH group. The resulting bond represents a 3′-5′ phosphodiester bond.
Function, action, and roles
Endonucleases contribute to the processing of DNA and RNA. The nucleic acids adenine, thymine, guanine, and cytosine form the genetic code, which not only passes information to the next generation during inheritance but also controls cell metabolism. The sequence of the various nucleic acids in the DNA codes the order in which other enzymes – known as ribosomes – chain amino acids together. All proteins are made up of these chains; accordingly, the sequence of amino acids in a protein depends on the sequence of nucleic acids in the DNA – which in turn determines the shape and function of the protein. Biology refers to the translation of the genetic code into amino acid chains as translation. Translation takes place in the cells of the human body outside the cell nucleus – but the DNA is located exclusively inside the cell nucleus. Therefore, the cell must make a copy of the DNA. The sugar molecule used in the copy is not deoxyribose, but ribose. Therefore, it is an RNA. In biology, the production of RNA is also called transcription and requires endonucleases. In the course of translation, various enzymes must extend the chain of nucleotides. Partial cleavage by endonucleases also makes this possible. Endonucleases also have the same function in replication, when a copy of DNA is required as part of cell division.
Formation, occurrence, properties, and optimal levels
Endonucleases, like all enzymes, are proteins composed of chains of amino acids. All amino acids have the same basic structure: they consist of a central carbon atom to which an amino group, a carboxyl group, a single hydrogen atom, an α-carbon atom, and a residue group are attached. The residue is characteristic of each amino acid and determines which interactions it can form with other amino acids and other substances. The one-dimensional structure of enzymes in the form of their amino acid chain is also called primary structure in biology. Foldings occur within the chain; other enzymes catalyze this process. The spatial order is stabilized by hydrogen bonds that form between the individual building blocks. This secondary structure can appear as both an α-helix and a β-fold. The secondary structure of the protein folds further and takes on more complex shapes. Here, the interactions between the different amino acid residues play the crucial role. Due to biochemical properties of the respective residues, the tertiary structure finally emerges. Only in this form does the protein have its final properties, which depend to a large extent on its spatial shape. In the case of an enzyme, this shape includes the active site, where the actual enzyme reaction takes place. In the case of endonucleases, the active site reacts with DNA or RNA as substrate.
Diseases and disorders
Endonucleases play an important role in the repair of DNA by breaking down its chains. Repair is necessary when DNA has been damaged by radiation or chemical substances, for example.Even UV light can have this effect. An increased dose of UV-B radiation results in the accumulation of thymine dimers in the DNA strand. They deform the DNA and subsequently lead to disruptions in the duplication of the DNA: the enzyme that reads out the DNA during replication cannot get past the deformation caused by thymine dimers and therefore cannot continue its work. Human cells have various repair mechanisms. Excision repair involves the use of endonucleases. A specialized endonuclease is able to recognize thymine dimers and other damage. It cuts the affected DNA strand twice, both before and after the defective site. Although this removes the dimer, it creates a gap in the code. Another enzyme, DNA polymerase, must then fill the gap. As a comparison, it draws on the complementary DNA strand and adds the appropriate base pairs until the gap is filled and the damaged DNA strand is restored. This repair is not rare, but occurs many times a day in the body. Disturbances in the repair process can lead to various disorders, for example the skin disease xeroderma pigmentosum. In this disease, affected individuals are overly sensitive to sunlight because the cells are unable to repair UV damage.
