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Mutations Caused By Antibiotics

BY: Zandro Cabaral | Category: Bioinformatics | Submitted: 2011-01-29 20:14:43
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Article Summary: "Mutations are the result of changes in the messenger RNA codon nucleotide sequence. The shift in the reading frame of the entire DNA chain after the mutation is called a Frameshift mutation..."

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Mutations are the result of changes in the messenger RNA codon nucleotide sequence. The shift in the reading frame of the entire DNA chain after the mutation is called a Frameshift mutation. The loss of a single base either spontaneously or due to damage is called a Deletion Mutation. An Insertion Mutation happens when Acridine intercalates between adjacent DNA nitrogen bases and gets read by RNA polymerase causing the addition of extra bases into the new messenger RNA. A Transition mutation is either when a purine is substituted by a purine or when a pyrimidine is substituted by a pyrimidine. A Transversion mutation is either the substitution of a purine for a pyrimidine or the substitution of a pyrimidine for a purine. A Missense Mutation it changes codon to another codon for a different amino acid. If the new amino acid is similar to the old one the synthesized protein might function.

Many antibiotics are selectively toxic to either eukaryotic or prokaryotic organisms because they interfere with specific enzymes of DNA, RNA, or protein synthesis.There are antibiotics that inhibit the protein synthesis in the 30S ribosomal subunit. Aminoglycosides bind to prokaryotic 30S ribosomal subunit and cause misreading which prevent the initiation of protein synthesis. Tetracycline binds to the acceptor site on the prokaryotic 30S subunit preventing it from binding the activated amino acid-transfer RNA complex. There are also antibiotics that inhibit protein synthesis at the 50S ribosomal subunit. These are the Chloramphenicol which binds to prokaryotic 50S subunit and inhibits peptidyl-transferase and Erythromycin and Clindamycin which both bind to the 23S ribosomal RNA within the prokaryotic 50S subunit and prevent translocation. Cycloheximide binds to the eukaryotic 60S subunit and inhibits peptidyltransferase. Puromycin is an amino acid analog that binds to the A site and has an amino group which can form a peptide bond. No further elongation can take place, and protein synthesis of both prokaryotes and eukaryotes is inhibited. Diphtheria toxin inhibits eukaryotic elongation factor 2; interrupting eukaryotic protein synthesis.

Antibiotics can also inhibit RNA synthesis. Drugs of this kind are: Actinomycin which binds to double stranded DNA so that RNA polymerase cannot read it, Rifampin which binds to the Beta subunit of RNA polymerase and inhibits the start of transcription and Amanita phylloides, the "Angel of Death" mushroom produces a toxin which inhibits RNA polymerase II stopping mRNA production.
Quinolones bind to and inhibit DNA gyrase preventing DNA synthesis. Nalidixic acid and Novobiocin both inhibit DNA topoisomerase, stopping DNA synthesis. These drugs inhibit DNA synthesis. Some drugs inhibit nucleic acids in other ways. One is Methotrexate, an analog of folic acid that is a competitive inhibitor of dihydrofolate reductase. Therefore, it inhibits deoxythymidylate synthesis. Aminoprotein is an analog of folic acid and a competitive inhibitor of dihydrofolate reductase. Therefore, it inhibits deoxythymidylate synthesis. The 5-flourouracyl is another drug. This drug inhibits thymidylate synthase and inhibits deoxythymidylate synthesis. Puromycin binds to the A site and inhibits protein synthesis irreversibly.

The nucleotide in the 3rd position has less influence on which amino acid a codon specifies. For example, the codons CUU, CUC, CUA, and CUG all code for the amino acid leucine; this is called Wobble. Notice that while each 3 nucleotide sequence codes for only one kind of amino acid like CUA always codes for leucine, other codons can still code for that amino acid. The genetic code is called degenerate, since more than one codon can specify a given amino acid. It usually does not matter what base is in the third position.

The genes may mutate or repaired. The mechanisms of DNA and RNA repair are agents that are formed in the body to protect these nucleic acids. The Nitrous Acid is an alkylating agent produced in cells by metabolism of nitrites and nitrates which are often used as food reservatives. The Cytosine can spontaneously lose its -NH3 group forming uracil. Mutant Base Endonucleases is a group of enzymes each of which recognize and remove a specific mutant base containing nucleotides and the Mutant Base Glycosylases are enzymes which recognize and remove specific mutant nitrogen bases from their deoxyribose. The U.V. endonuclease removes pyrimidine-pyrimidine dimers that occur, usually between two thymines, in the same strand due to exposure to ultraviolet light. Then polymerase I or alpha fills in the gap with the appropriate nucleotides. Dimers can lead to mutations. Therefore, finding the mistake and repairing it is important.

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