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Arthur Kornberg and his fellow scientists devoted decades to unravel the secrets behind how DNA made its new, complementary strand. Upon learning about the different enzymes that are involved in catalyzing the DNA synthesis mechanism of three coliphages using the cellular machinery of Escherichia coli, they also discovered that there is one particular enzyme that acted similar to RNA polymerase… except that it was different. They learnt that unlike the good old RNA polymerase, this enzyme was found to be resistant to the most infamous RNA polymerase inhibitors, mainly rifampicin. Initially calling it rifampicin-resistant RNA polymerase, the scientists also discovered that DNA synthesis of the coliphage G4 was dependent upon addition of this enzyme. Furthermore, this enzyme was only able to transcribe specific region of the DNA to synthesise a small RNA fragment, which we now know as the RNA primer. Since this discovery, the scientists agreed to rename this enzyme primase. Primase was subsequently identified in other organisms, such as Drosophila melanogaster, which is a model organism for eukaryotes. They learnt that primase works hand-in-hand with DNA polymerase α to synthesise DNA in the fruit fly. The discovery of primase helped us piece together this huge puzzle that is the mechanism of DNA replication. Not only that, it has recently been discovered that primase and DNA polymerase might form a subunit in human. The scientists figured out that strange activities of this enzyme subunit might be an underlying cause for human cancer. An idea that this subunit can be used as a novel cancer biomarker as well as targeted therapeutics was then born from this finding.
Creator: Sharra Liando
References:
A possible role for RNA polymerase in the initiation of M13 DNA synthesis. Brutlag D, Schekman R, Kornberg A. Proceedings of the National Academy of Sciences. 1971 Nov; 68(11):2826-9. doi: 10.1073/pnas.68.11.2826
Initiation of DNA synthesis: synthesis of ΦX174 replicative form requires RNA synthesis resistant to rifampicin. Schekman R, Wickner W, Westergaard O, Brutlag D, Geider K, Bertsch LL, Kornberg A. Proceedings of the National Academy of Sciences. 1972 Sep; 69(9): 2691-5. doi:10.1073/pnas.69.9.2691
Replication of phage G4. A novel and simple system for the initiation of deoxyribonucleic acid synthesis. Zechel K, Bouché J, Kornberg A. The Journal of Biological Chemistry. 1975 Jun 25; 250(12): 4684-9. doi: 10.1016/S0021-9258(19)41355-0
dnaG gene product, a rifampicin-resistant RNA polymerase, initiates the conversion of a single-stranded coliphage DNA to its duplex replicative form. Bouché J, Zechel K, Kornberg A. The Journal of Biological Chemistry. 1975 Aug 10; 250(15): 5995-6001. doi: 10.1016/S0021-9258(19)41148-4
Primase, the dnaG protein of Escherichia coli. An enzyme which starts DNA chains. Rowen L, Kornberg A. The Journal of Biological Chemistry. 1978 Feb 10;253(3): 758-764. doi: 10.1016/S0021-9258(17)38167-X.
A DNA primase activity associated with DNA polymerase alpha from Drosophila melanogaster embryos. Conaway RC & Lehman IR. Proceedings of the National Academy of Sciences. 1982 Apr 1;79(8): 2523-7. doi: 10.1073/pnas.79.8.2523
Multi-omics analysis of DNA replication-associated primase polymerase (PRIMPOL) in pan-cancer: a potential target for prognosis and immune response. Deng L, Thakur A, Peng J, Song L, Li Z. European Journal of Medical Research. 2023 Jun 30;28(1): 207. doi: 10.1186/s40001-023-01181-9
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