The Discovery of Error-prone DNA Polymerase V and its Unique Regulation by RecA and ATP [Enzymology]

August 26th, 2014 by Goodman, M. F.

My career pathway has taken a circuitous route beginning with a Ph.D. in electrical engineering from Johns Hopkins University, followed by five postdoctoral years in biology at Hopkins and culminating in a faculty position in Biological Sciences at the University of Southern California. My startup package in 1973 consisted of $2,500, not to be spent all at once, plus an ancient Packard scintillation counter that had a series of rapidly flashing light bulbs to indicate a radioactive readout in counts/min. My research pathway has been similarly circuitous. The discovery of Escherichia coli DNA polymerase V began with an attempt to identify the mutagenic DNA polymerase responsible for copying damaged DNA as part of the well-known SOS regulon. While we succeeded in identifying a DNA polymerase, one that was induced as part of the SOS response, we actually rediscovered DNA polymerase II, albeit in a new role. A decade later we discovered a new polymerase, DNA polymerase V whose activity turned out to be regulated by bound molecules of RecA protein and ATP. This "Reflections" article describes our research trajectory, includes a review of key features of DNA damage-induced SOS mutagenesis leading us to pol V and reflects on some of the principal researchers who've made indispensable contributions to our efforts.