DNA damage is a chemical alteration occurring in the structure of DNA due to mutation. Some agents associated with the mutation are ultraviolet UV radiations, chemotherapeutic drugs for cancer, environmental mutagens, and smoking. Nucleotide excision repair (NER) represents a type of DNA mechanism that works like a cut and patch mechanism. A short stretch of damaged DNA is cut and removed. The gap is refilled with the new correct nucleotide. NER is present in both prokaryotes and eukaryotes each having a separate set of enzymes. In eukaryotes, NER is complex while it is simple in prokaryotes.
All living organisms consist of DNA which is a double helical structure carrying the genetic material that carries the essential information.
Any damage associated with DNA occurring because of several chemicals ï€¨aromatic aminesï€©and physical ï€¨ultraviolet radiationï€©agents is termed as mutation.
A DNA forms adduct by covalently binding to chemotherapeutic drugs used for treating cancer. Cigarette smoking is also another major cause of DNA damage that occurs due to carcinogens such as benzopyrene.
DNA directly absorbs UVB photons from sunlight. When two thymine nucleotides are nearby, the thymine residues stick together to form the thymine-thymine dimers.
NER enzymes commonly recognize the damage produced on DNA involving thymine dimers caused due to UV radiation and benzopyrene – guanine adducts caused due to smoking. This repair mechanism almost removes and replaces 30 bases in a length of damaged DNA. The general mechanism of NER includes the following steps such as;
Recognition of DNA damage:The UV radiation produces damage on the DNA to form thymine-thymine dimers and other bulky adducts formed by aromatic mutagenic compounds.
Removal of fragments of DNA:The DNA is unwinded by specific enzymes having helicase activity. Specific damaged regions on DNA are recognized by specific enzymes. The regions near the damage are excised.
DNA synthesis:The removed nucleotides are added by the enzyme DNA polymerase I.
DNA ligation:An enzyme DNA ligase seals the damaged DNA regions.
In prokaryotes: In prokaryotes such as bacteria, the repair pathway is initiated by the UvrABC endonuclease complex. This complex has four key enzymes namely UvrA, UvrB, UvrC, and UvrD. The word Uvr represents ultraviolet radiation. UvrD has helicase activity which unwinds the double-helical strand. The UvrA recognizes the damaged DNA. The UvrB and UvrC are involved in eliminating the nucleotides that are damaged on the DNA strand. These enzymes are a special type of endonucleases that cuts two phosphodiester bonds simultaneously. Enzyme DNA polymerase I fill the gap by adding new nucleotides after removal of the damaged ones. The enzyme DNA ligase forms the phosphodiester bond resealing the nicks on the DNA strand.
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