Chemical Forums
Specialty Chemistry Forums => Biochemistry and Chemical Biology Forum => Topic started by: Soverdu on April 10, 2014, 05:40:54 PM
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In DNA synthesis DNA polymerase can only add new nucleotides to a preexisting 3' OH-group a so called primer end. This is because the -OH is needed to start the reaction mechanism by making a nucleophilic attack on the triphosphate.
But RNA polymerase does not need the primer in RNA synthesis. Why is this? Is it because the enzyme itself makes the nucleophilic attack or what happens?
Thanks,
Soverdu
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If the enzyme made the nucleophilic attack, would it actually be an enzyme?
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If the enzyme made the nucleophilic attack, would it actually be an enzyme?
I suppose it would. Isn't that what is called covalent catalysis? Then it would obviously have to leave the nucleotide again and be reduced somehow. Or maybe it could just loose a R-OH group to the nucleotide and then regenerate it later.
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It is not unreasonable to think that de novo synthesis could occur by the enzyme itself providing the nucleophile for the addition of the first nucleotide. There are, in fact, examples of protein-primed DNA synthesis (http://www.annualreviews.org/doi/abs/10.1146/annurev.bi.60.070191.000351) where the nucleophile to which DNA polymerase adds the first nucleotide is a protein, not the 3' OH of an existing nucleic acid.
RNA polymerase, however, does not utilize a protein priming mechanism for the initiation of de novo RNA synthesis. Rather, RNA polymerases contain pockets – distinct from the nucleotide binding pockets used during processive primer extension – capable of binding a pair of nucleotides and linking them together to form the nascent RNA chain.
Why would RNA polymerase have this ability yet DNA polymerases lack this ability? Well, according to the "RNA world" hypothesis, RNA preceded DNA as the genetic material, so the first nucleic acid synthesizing enzymes to evolve would have been the RNA polymerases, and these enzymes would have needed to carry out de novo synthesis in order to make nucleic acids. Thus, when DNA polymerases emerged later during evolution (DNA polymerases are evolutionarily distinct from most RNA polymerases), the RNA polymerases were already capable of synthesizing primers, so the DNA polymerases may never have needed to evolve the ability to perform de novo synthesis.