RNA Priming of DNA Replication
Abstract
The purpose of this essay is to review the development of our current understanding of what was, until 1971, the enigma of DNA chain initiation. It is now proposed that the start of a DNA chain is primed by a short RNA transcript. Synthesized by an RNA polymerase, the transcript is covalently extended by DNA polymerase action and later removed from the DNA. This mechanism has been demonstrated in vitro for the start of DNA chains in some prokaryotic and eukaryotic systems and is an attractive model for others. This essay will focus on RNA polymerase action in the priming event.
COMPARISON OF DNA AND RNA POLYMERASES
The basic elements in the synthesis of a nucleic acid are the same whether the chain produced is DNA or RNA or whether template directions are taken from DNA or RNA (Kornberg 1974). DNA polymerases probably follow these directions with greater fidelity than do RNA polymerases, but the most profound difference between them is in the capacity to initiate a new chain.
Among the many DNA polymerases of viral, bacterial and animal origins, none can start a chain in vitro. An RNA polymerase by contrast is designed to start chains. The essence of transcription is the selective copying of passages from the chromosome record starting at a promoter. Thus DNA polymerases, remarkable for their error-free copying of the entire chromosome, are apparently blind to initiation signals, including the one promoting the origin of a replication cycle. In addition, at least some DNA...
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PDFDOI: http://dx.doi.org/10.1101/0.331-352