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The central dogma of molecular biology was first enunciated by '' paper published in 1970 :Crick, F. (1970): Central Dogma of Molecular Biology. Nature 227, 561-563. PMID 4913914 The central dogma of Molecular Biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred back from protein to either protein or nucleic acid. In other words, 'once information gets into protein, it can't flow back to nucleic acid.' The dogma is a framework for understanding the transfer of ), DNA information can be copied into MRNA , ( Transcription ), and proteins can be synthesized using the information in mRNA as a template ( Translation ). BIOLOGICAL SEQUENCE INFORMATION Main article: Primary Structure Biopolymers are biological , or arrangement of their monomers, effectively encodes information. The transfers of information described by the central dogma are faithful, Deterministic transfers, wherein one biopolymer's sequence is used as a template for the construction of another biopolymer with a sequence that is entirely dependent on the original biopolymer's. GENERAL TRANSFERS OF BIOLOGICAL SEQUENTIAL INFORMATION DNA Replication See Also: DNA replication As the final step in the Central Dogma, to transmit the genetic information between parents and progeny, the DNA must be replicated faithfully. Replication is carried out by a complex group of proteins that unwind the Superhelix , unwind the Double-stranded DNA Helix , and, using DNA Polymerase and its associated proteins, copy or Replicate the master template itself so the cycle can repeat DNA → RNA → protein in a new generation of cells or organisms. Transcription See Also: Transcription (genetics) Transcription is the process by which the information contained in a section of DNA is transferred to a newly assembled piece of Messenger RNA (mRNA). It is facilitated by RNA Polymerase and Transcription Factor s. In Eukaryote cells the primary transcript (pre-mRNA) is often processed further via Alternative Splicing . In this process, blocks of mRNA are cut out and rearranged, to produce different arrangements of the original sequence. Translation See Also: Translation (genetics) Eventually, this mature mRNA finds its way to a Ribosome , where it is Translated . In Prokaryotic cells, which have no nuclear compartment, the process of transcription and translation may be linked together. In Eukaryotic cells, the site of transcription (the Cell Nucleus ) is usually separated from the site of translation (the Cytoplasm ), so the mRNA must be transported out of the nucleus into the cytoplasm, where it can be bound by ribosomes. The mRNA is read by the ribosome as triplet Codon s, usually beginning with an AUG, or initiator methonine codon downstream of the Ribosome binding site. Complexes of Initiation Factor s and Elongation Factor s bring Aminoacylated Transfer RNA s (tRNAs) into the ribosome-mRNA complex, matching the codon in the mRNA to the anti-codon in the tRNA, thereby adding the correct Amino Acid in the sequence encoding the gene. As the amino acids are linked into the growing peptide chain, they begin folding into the correct conformation. This folding continues until the nascent polypeptide chains are released from the ribosome as a mature protein. In some cases the new polypeptide chain requires additional processing to make a mature protein. The correct folding process is quite complex and may require other proteins, called Chaperone Protein s. Occasionally proteins themselves can be further spliced, when this happens the inside "discarded" section is known as an Intein . SPECIAL TRANSFERS OF BIOLOGICAL SEQUENTIAL INFORMATION Reverse transcription See Also: Reverse transcription Reverse transcription is the transfer of information from RNA to DNA (the reverse of normal transcription). This is known to occur in the case of Retrovirus es, such as HIV , and, in higher Eukaryote s, in the case of Retrotransposon s. It is not, however, the general case in most living organisms. RNA replication RNA replication is the copying of one RNA to another. It is possible that this is the mechanism by which some RNA Virus es replicate. Direct translation from DNA to protein Direct translation from DNA to protein has been demonstrated in a cell-free system (i.e. in a test tube), using extracts from ''E. Coli'' that contained ribosomes, but not intact cells. These cell fragments could express proteins from foreign DNA templates, and Neomycin was found to enhance this effect. 1 METHYLATION Variation in Methylation states of DNA can alter gene expression levels significantly. Methylation variation usually occurs through the action of DNA methylases (which are proteins). When the change is heritable, it is considered Epigenetic . When the change in information status is not heritable, it would be a Somatic Epitype . The effective information content has been changed by means of the actions of a protein or proteins on DNA, but the primary DNA sequence is not altered. PRIONS - ALMOST AN "UNKNOWN TRANSFER" Prion s are proteins that propagate themselves by making conformational changes in other molecules of the same type of protein. This change affects the behaviour of the protein. In Fungi this change can be passed from one generation to the next, i.e. Protein → Protein. Although this represents a transfer of information, it is not an exception to the central dogma, since the sequence of the protein remains unchanged. USE OF THE TERM "DOGMA" In his Autobiography , '' What Mad Pursuit '', Crick wrote about his choice of the word '' Dogma '' and some of the problems it caused him: I called this idea the central dogma, for two reasons, I suspect. I had already used the obvious word Hypothesis in the sequence hypothesis, and in addition I wanted to suggest that this new assumption was more central and more powerful. ... As it turned out, the use of the word dogma caused almost more trouble than it was worth.... Many years later Jacques Monod pointed out to me that I did not appear to understand the correct use of the word dogma, which is a belief that cannot be doubted. I did apprehend this in a vague sort of way but since I thought that all religious beliefs were without foundation, I used the word the way I myself thought about it, not as most of the world does, and simply applied it to a grand hypothesis that, however plausible, had little direct experimental support. Similarly, Horace Freeland Judson records in ''The Eighth Day of Creation'':2 "My mind was, that a dogma was an idea for which there was ''no reasonable evidence''. You see?!" And Crick gave a roar of delight. "I just didn't ''know'' what dogma ''meant''. And I could just as well have called it the 'Central Hypothesis,' or — you know. Which is what I meant to say. Dogma was just a catch phrase." CRITICISMS OF THE USE OF THE CENTRAL DOGMA AS A RESEARCH STRATEGY Some researchers in the area of Systems Biology claim that scientists sometimes misuse the central dogma as a research strategy. They claim that an uncritical reading of the central dogma could inhibit novel approaches to understanding multicellular development of organisms as well as multicellular diseases; that the central dogma is often used as a Reductionist research strategy that proceeds bottom up, attempting to explain all biological phenomena in molecular terms. Although they don't dispute the very specific reading of the central dogma, these researchers claim that a reductionist research strategy may limit the understanding of complex systems that cannot be analyzed by their molecular interactions alone because of the combinatorial complexity involved.Werner, E. (2005): Genome Semantics, In Silico Multicellular Systems and the Central Dogma. FEBS Letters 579, 1779-1782. PMID 15763551 SEE ALSO REFERENCES FURTHER READING EXTERNAL LINKS
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