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In Memoriam: E. Peter Geiduschek, 1928-2022

May 4, 2022

By James T. Kadonaga

E. Peter Geiduschek

E. Peter Geiduschek was born in Vienna, Austria and went to secondary school in St. Albans, England, college at Columbia University and graduate school at Harvard University. He served in the U.S. Army. Peter came to UC San Diego in 1970 from the University of Chicago and retired from campus activities in 2014.

Peter was a truly extraordinary scientist and individual (see his autobiography in the Annual Review of Biochemistry). For his colleagues in Biology, he was the role model for scientific excellence, leadership, fellowship, and integrity. He was the foundation, as well as the star, of molecular biology at UC San Diego. His many honors include membership in the National Academy of Sciences and the American Academy of Arts and Sciences.

In his career, Peter provided a remarkable proportion of the fundamental knowledge of DNA structure and gene regulation that is now taught to students of molecular biology. In the decade marked by the discovery of the double helical structure of DNA, he began a series of seminal studies on the physical properties of DNA. His major contributions in the late 1950s and early 1960s include: (1) the first direct measurement of the heat of denaturation of DNA; (2) the role of water in the stability of the DNA double helix (the now commonly used term "chaotropic" was coined by Peter to describe salts that destabilize DNA by disordering water); (3) that, in addition to hydrogen bonding (between A:T and G:C base pairs), hydrophobic forces played an important role in the stability of the double helix; and (4) the demonstration that DNA denaturation (strand separation) was fully reversible (although it was thought not to be at the time).

Then, Peter embarked upon studies of transcription—the synthesis of RNA from the DNA template. His early studies in this area, which were in collaboration with Samuel Weiss, include the conclusive demonstration that RNA synthesized in vitro is entirely and faithfully complementary to the DNA template sequence and that the DNA helix does not unwind completely during transcription as it does in DNA replication. In a landmark paper, Peter demonstrated that transcription of bacteriophage DNA in bacteria was asymmetric (only one DNA strand was copied into RNA). This latter finding implied that there is directional specificity in the transcription process and foreshadowed the existence of promoters.

In the late 1960s, Peter began to use the bacteriophage T4 as a model for transcriptional regulation. These studies provided many key discoveries that include alternative sigma factors, the coupling of late phage transcription to DNA replication and activation of transcription by a fascinating doughnut-shaped protein clamp that slides along DNA (with the DNA in the center of the "doughnut"). These findings are an important part of our current knowledge of gene regulation.

In the mid 1980s, Peter initiated a new project on transcription by RNA polymerase III in the yeast, Saccharomyces cerevisiae. His many contributions to eukaryotic transcription include the fractionation and purification of the factors that mediate RNA polymerase III transcription, the identification of TFIIIB as the key factor that directs transcription by RNA polymerase III and the development and use of photo-crosslinking techniques for the analysis of the sequence-specific binding of proteins to DNA. This work provided an immense amount of clarity to this complicated yet important process.

Hence, Peter was a true pioneer of DNA structure and gene expression. He was among the first scientists to analyze transcription by RNA polymerase, and he carried out innovative and elegant biochemical studies that elucidated the roles of proteins required for gene expression in bacterial viruses and in eukaryotic cells. His studies provided key insights into the molecular mechanisms by which viruses take over the host synthetic machinery, and by which they control the timing of the expression of their genes to ensure efficient multiplication. These studies are of fundamental importance to our understanding of gene expression and of the multiplication of human viruses.

He additionally was a major force behind the discovery and analysis of the factors and mechanisms involved in the synthesis of tRNAs by RNA polymerase III. It should further be noted that Peter's research was carried out with such a level of artistry and elegance that he truly achieved a convergence of science and art in his work.

Peter was also uniquely notable for his participation in the departmental seminar program. In the question-and-answer period after each seminar, he would wait until all of the "regular" questions were discussed. He would then carefully ask an incisive question on the most critically important shortcoming of the presented research. In each seminar, this was a highly anticipated moment for all of the other local attendees. It was also a moment that was feared by visiting speakers who knew of this ritual.

E. Peter Geiduschek was a leader and a role model for undergraduate students, graduate students, postdocs and his fellow faculty. He was a major driving force behind the excellence of science in biology at UC San Diego. Moreover, with his wit, charm and warm and caring personality, he was a much-loved colleague. We thus honor and will fondly remember a remarkable and singular individual who has provided much of the basic knowledge of DNA and gene expression that we enjoy today and significantly and selflessly contributed to the establishment of UC San Diego as one of the premier research universities in the world.

By James T. Kadonaga, on behalf of the Department of Molecular Biology and the School of Biological Sciences