Скачать с ютуб 5-Bromouracil: villian or hero? Mutagenesis with 5-bromouracil in bacteriophages в хорошем качестве

5-Bromouracil: villian or hero? Mutagenesis with 5-bromouracil in bacteriophages

OTHER VIDEOS YOU MIGHT LIKE: • X-rays in action: Unveiling genetic mutation by ionising radiation -    • X-rays in action: Unveiling genetic m...   • The past, present and future of molecular phylogenetics -    • The past, present and future of molec...   • The structure of RNA polymerase I: A 50 year mystery solved! -    • The structure of RNA polymerase I: A ...   Within genetics, 5-bromouracil plays dual roles – a genetic trickster and potential antiviral treatment. But how? The story begins with Watson and Crick who determined the structure of DNA in 1953. The base pairing between the four nucleotides ensures the stability of this structure and their specific sequence are the instructions of all life. However, mutagenic base analogs can disrupt this ordered sequence and lead to DNA mutations. 5-bromouracil is an analog of thymine and is formed by replacing the methyl group on the fifth carbon with bromine. The mutagenic properties of 5-bromouracil were first observed by the inhibition of growth in Lactobacillus casei bacteria when 5-bromouracil was added to the medium. This lay the foundations for Litman and Pardee who were determined to uncover 5-bromouracil’s mutagenic effects within bacteriophages. In 1956, they conducted a groundbreaking experiment by growing E. coli bacteria in a medium containing sulphanilamide and 5-bromouracil. They then infected T2 bacteriophages into the medium and plated the culture at various concentrations of 5-bromouracil to determine if there was a concentration-dependant relationship. Notably, mutant plaques were revealed which were areas of bacterial cell death smaller than the wild-type plaques. Along with the confirmed concentration-dependant relationship, it was clear 5-bromouracil altered the viral genome by reducing the fitness and replication efficiency. The mechanism was hypothesised by Litman and Pardee to be competitive binding with thymine as they noticed sulphanilamide (which limits thymine synthesis) was essential for mutant plaque production. This was confirmed by multiple researchers who determined 5-bromouracil to exist in a keto form which binds with adenine and an enol form which binds with guanine. The tautomeric shifting results in A-T to G-C transitions during replication, significantly disrupting DNA structure and metabolism. Emerging research shows the possibility for 5-bromouracil to be used in human antiviral medication and this was catalysed by Litman and Pardee’s experiment which provided evidence for the mutagenesis of 5-bromouracil in bacteriophages. Creator: Isabella Atkinson References: Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Watson JD, Crick FHC. Nature. 1953 Apr 25;248(5451):765. doi: 10.1038/248765a0. Studies on analogs of purines and pyrimidines. Hitchings GH, Elion GB, Falco EA, Russel PB, Vanderwherf H. Ann N Y Acad Sci. 1950 Jul 7;52(8):1318-35. doi: 10.1111/j.1749-6632.1950.tb54032.x. Incorporation of halogenated pyrimidines into the deoxyribonucleic acids of Bacterium coli and its bacteriophages. Dunn DB, Smith JD. Nature. 174:305-6. doi: 10.1038/174305a0. Production of bacteriophage mutants by a disturbance of deoxyribonucleic acid metabolism. Litman RM, Pardee AB. Nature. 1956 Sep 8;178(4532):529-31. doi: 10.1038/178529b0 Incorporation of halogenated pyrimidines into the deoxyribonucleic Acids of Bacterium coli and its Bacteriophages. Zamenhof S, Griboff G. Nature 174, 306–307 (1954). https://doi.org/10.1038/174306a0 The specific mutagenic effect of base analogues on phage T4. Freese E. J Mol Biol. 1958 Dec 3;1(2):87-105. doi: 10.1016/S0022-2836(59)80038-3 The induction of mutants of bacteriophage T2 by 5-bromouracil. III. Nutritional and structural evidence regarding mutagenic action. Litman RM, Pardee AB. Biochim Biophys Acta. 1960 Jul 29;42:117-30. doi: 10.1016/0006-3002(60)90758-7. The mechanism of 5-bromouracil mutagenesis in the bacteriophage T alpha. Terzaghi BE, Streisinger G, Stahl FW. Proc Natl Acad Sci U S A. 1962 Sep 15;48(9):1519-24. doi: 10.1073/pnas.48.9.1519. Antiviral effect of guanidine and its derivatives. I. The inhibitory effect of guanidine on the multiplication of poliomyelitis virus in tissue culture. Ueda T, Toyoshima S, Seto Y, Tsuji T, Nomoto J. Keio J Med. 1961 Dec;10:257-65. doi: 10.2302/kjm.10.257.