Central dogma of molecular biology
Original Central Dogma (Genetics & Inherited Conditions)
Nobel Prize winner Francis Crick, who was codiscoverer with James Watson of the double helical structure of DNA, coined the term “central dogma” in 1958 to describe the fact that the processing of genetic information contained in DNA proceeded unidirectionally by its conversion first to an RNA copy, called messenger RNA (mRNA), in a molecular process called transcription. Then the genetic information contained in the sequence of bases in the mRNA was read in the ribosome, and the appropriate amino acids carried by transfer RNAs (tRNAs) were assembled into protein according to the genetic code in a process called translation. The basis of these reactions stemmed from the properties of DNA, particularly its double helical structure. The fact that the two strands of DNA were held together by hydrogen bonds between specific nucleic acid bases (guanine-cytosine, adenine-thymine) on the two strands clearly suggested how the molecule could be duplicated. Watson and Crick postulated that if they split the double-stranded structure at the hydrogen bonds, attached new complementary bases, and reformed the hydrogen bonds, precise copies identical to the original DNA would result. In an analogous manner, RNA was produced by using one DNA strand as a template and adding the correct complementary bases according to what came to be called Watson Crick base pairing. Thus the original dogma stated that transfer of genetic information...
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Modified Central Dogma (Genetics & Inherited Conditions)
Several discoveries made it necessary to change the central dogma. The first and most heretical information came from the study of retroviruses, including the human immunodeficiency virus (HIV). Howard Temin reported that viruses of this group contained an enzyme called reverse transcriptase, which was capable of converting RNA to DNA and thus challenging the whole basis of molecular reactions and the central dogma. Temin and David Baltimore were subsequently awarded Nobel Prizes for their work describing this new enzyme. They were able to show that it synthesizes a DNA strand complementary to the RNA template, and then the DNA-RNA hybrid is converted to a DNA-DNA molecule, which inserts into the host chromosome. Only then can transcription and translation take place.
The second significant change was finding that RNA can act as a template for its own synthesis. This situation occurs in RNA bacteriophages such as MS2 and QB. These phages are very simple, with genomes specifying only three proteins, a coat and attachment proteins and an RNA replicase subunit. This subunit combines with three host proteins to form the mature RNA replicase that catalyzes the replication of the single-stranded RNA. Thus translation to form the protein subunit of RNA replicase occurs using the RNA genome as mRNA upon viral infection without transcription taking place. Only then is the RNA template successfully replicated.
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Importance and Applications (Genetics & Inherited Conditions)
The theoretical importance of the central dogma is unquestioned. For example, one modern-day scourge, the human immunodeficiency virus(HIV), replicates its genetic material by reverse transcription (central dogma modification), and one of the drugs shown to contain this virus, azidothymidine (AZT), targets the reverse transcriptase enzyme. Perhaps even more important is the use of the reverse transcription polymerase chain reaction (RT-PCR), one application of the polymerase chain reaction originally devised in 1983 by Kary B. Mullis, formerly of Cetus Corporation. RT-PCR employs reverse transcriptase to form a double-stranded molecule from RNA, resulting in a revolutionary technique that can generate usable amounts of DNA from extremely small quantities of DNA or from poor-quality DNA. Also of practical importance is the laboratory modification of hammerhead ribozymes (central dogma modification), found naturally in plant pathogens, for clinical uses, such as to target RNA viruses infecting patients, including HIV and papillomavirus.
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Further Reading (Genetics & Inherited Conditions)
Allison, Lizabeth A. “From Gene to Protein.” In Fundamental Molecular Biology. Malden, Mass.: Blackwell, 2007. This chapter’s explanation of how DNA produces proteins includes information about the central dogma.
Cech, T. R. “RNA as an Enzyme.” Scientific American 255, no. 5 (November, 1986): 64-75. A Nobel Prize winner describes his revolutionary discovery that RNA can catalyze reactions. Includes both charts and color illustrations.
Crick, F. “Central Dogma of Molecular Biology.” Nature 227, no. 5258 (August 8, 1970): 561-563. The seminal paper in which Nobel laureate Crick, a codiscoverer of DNA’s double helical structure, proposed his theory of how molecular reactions occur.
O’Connell, Joe, ed. RT-PCR Protocols. Totowa, N.J.: Humana Press, 2002. Collects several papers on the use of reverse transcription polymerase chain reaction in analysis of mRNA, quantitative methodologies, detection of RNA viruses, genetic analysis, and immunology. Tables, charts, index.
Ohtsuki, Takashi, and Masahiko Sisido. “The Central Dogma: From DNA to RNA, and to Protein.” In Automation in Proteomics and Genomics: An Engineering Case-Based Approach, edited by Gil Alterovitz, Roseann Benson, and Marco Ramoni. Hoboken, N.J.: John Wiley, 2009. Focuses on the molecules and bioprocesses that are related to protein biosynthesis.
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Web Sites of Interest (Genetics & Inherited Conditions)
Eastern Michigan University, Biology 301: Genetics. http://www.emunix.emich.edu/~rwinning/Genetics/transcr.htm. This online course about genetics includes three pages about genes and transcription, including an illustrated discussion of the central dogma.
Genetic Science Learning Center, University of Utah. http://learn.genetics.utah.edu/content/begin/dna. Offers information and activities about DNA, proteins, and protein synthesis.
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