Myron Goodman reflects on SOS error-prone DNA repair

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Read Goodman’s JBC article.

For most people, nothing goes the way they plan it, and the most unexpected things are liable to happen at any time. One person who can attest to that is Myron F. Goodman, a professor at the University of Southern California. In his recent “Reflections” article for the Journal of Biological Chemistry, Goodman recounts the education and career path that led him to the discovery of error-prone DNA polymerase V and its unique regulation by RecA and ATP.

“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,” Goodman explains.

Having trained primarily in physics and electrical engineering, Goodman was not exposed to biology until his Ph.D. thesis led him to study ATP hydrolysis. His project was titled “Selective hydrolysis of adenosine triphosphate resulting from the absorption of laser light in a stretching mode of the terminal phosphate group,” and he quips in his JBC article that he, at the very least, needed to learn how to measure ATP hydrolysis.

Myron GoodmanGoodman

Goodman was provided a lab bench to learn how to do this assay, and from there his interest in biology expanded to a point at which he could not look back. Upon receiving his Ph.D., Goodman chose a postdoc focusing on biochemical enzymology instead of taking a job in his original field.

In 1973, Goodman joined USC as a faculty member, and his research pathway was also circuitous. It began with an attempt to identify the mutagenic DNA polymerase responsible for copying damaged DNA as part of the well-known SOS regulon, which led to the discovery of E. coli DNA polymerase V. E. coli DNA polymerase V is a part of the Y family of enzymes that are referred to as translesion synthesis polymerases.

Goodman writes: “The path to the discovery of pol V is closely linked to more than 60 years of experiments and concepts in the area referred to as ‘SOS error-prone DNA repair.’”

Goodman’s “Reflections” highlights the discoveries that impacted the field the most. The SOS regulatory proteins of the system LexA and RecA were identified in the mid-1970s, and the discovery of the SOS mutagenesis genes umuC and umuD soon followed.

Goodman goes on to explain the various experiments his group conducted to understand SOS error-prone DNA repair from the late 1970s up till now. In 1998, Goodman’s lab conducted experiments that led to the discovery that the UmuD’2C mutagenic complex could be a new type of low-fidelity DNA polymerase. By 1999, this was unequivocally shown to be a DNA polymerase with the polymerase activity in the UmuC subunit. Next, the new Y polymerase
family was identified, and, as of now, 13 family members have been identified in various species.

Most recently, Goodman discovered that an intrinsic DNA-dependent ATPase regulates the polymerase V function. Prior to this, no such ATPase activity or autoregulatory mechanism had been found on a DNA polymerase.

Although Goodman notes that his research pathway has been circuitous, it has truly come full circle. His interest in biology began with a study of ATP hydrolysis, and his most recent contribution to the field was the identification of the first DNA polymerase to be regulated by ATPase activity.

Nicole ParkerNicole Parker joined the University of Maryland, Baltimore County, in the Meyeroff Scholarship Program in 2007. She earned a B.S. in biochemistry and molecular biology from UMBC and is currently completing her Ph.D. in biochemistry and molecular biology at the Johns Hopkins School of Public Health, where she studies the biological activity of the protein GDNF and its effect on the spermatogonial stem and progenitor cells.