Full text loading...
Chapter 4 : Reprint of Temin and Mizutani's 1970 Paper Reporting the Discovery of Reverse Transcriptase
Although experiments with metabolic inhibitors continued to provide evidence that Rous sarcoma virus (RSV) replicated via a DNA provirus, it was the discovery of a viral enzyme capable of carrying out the synthesis of DNA from an RNA template that finally led to widespread acceptance of the DNA provirus hypothesis in 1970. This paper by Temin and Mizutani, published together with a similar paper by David Baltimore, unambiguously demonstrated a biochemical mechanism for synthesis of the DNA provirus. The existence of RNA-dependent DNA polymerase clearly showed that the "central dogma" could be reversed and brought widespread acceptance of the new mode of information transfer that Howard Temin had predicted in 1964. The key to detecting reverse transcriptase was looking for the enzyme in virus particles rather than in cells. In addition, Temin and Mizutani had found that formation of the RSV provirus in infected cells did not require new protein synthesis following virus infection. Moreover, the virion DNA polymerase activity was dependent upon the presence of intact viral RNA, indicating that the virion enzyme catalyzed the synthesis of DNA from an RNA template. As Temin and Mizutani concluded in their paper, these results provided "strong evidence that the DNA provirus hypothesis is correct". They also pointed out that the discovery of reverse transcriptase not only had major implications for understanding viral carcinogenesis but would also change the way it is thought about information transfer in biological systems.