Novel Metabolic Pathways in Virus Infection: the Work of Seymour Cohen
Year: 2007
Type: article
Abstract: Virus-induced Acquisition of Metabolic Function. I. Enzymatic Formation of 5-Hydroxymethyldeoxycytidylate (Flaks, J. G., and Cohen, S. S. (1959) J. Biol. Chem. 234, 1501–1506) Virus-induced Acquisition of Metabolic Function. IV. Thymidylate Synthetase in Thymine-requiring Escherichia coli Infected by T2 and T5 Bacteriophages (Barner, H. D., and Cohen, S. S. (1959) J. Biol. Chem. 234, 2987–2991) Seymour Stanley Cohen was born in Brooklyn, New York in 1917. He received a B.S. from the City College of New York in 1936 and then began his graduate studies at Columbia University's College of Physicians and Surgeons with Journal of Biological Chemistry (JBC) Classics author Erwin Chargaff (1Vischer E. Chargaff E. J. Biol. Chem. 1948; 176: 703-714http://www.jbc.org/cgi/content/full/280/24/e21Abstract Full Text PDF PubMed Google Scholar). Cohen's first paper on lysophosphatides was published in the JBC in 1939 (2Chargaff E. Cohen S.S. On lysophosphatides.J. Biol. Chem. 1939; 129: 619-628Abstract Full Text PDF Google Scholar), and subsequent studies, including components of his doctoral dissertation titled “The Thromboplastic Protein from Lungs,” also appeared in the JBC. Cohen received his Ph.D in 1941 and then did a postdoctoral fellowship at the Rockefeller Institute, where he worked with Wendell M. Stanley on plant viruses. He returned to Columbia University in 1942 and worked for a year as a research associate in biochemistry. In 1943, Cohen left New York for the University of Pennsylvania and became Instructor in Pediatrics at the University of Pennsylvania's Children's Hospital in 1945. He was subsequently named Assistant Professor of Biochemistry in Pediatrics in 1947, then Associate Professor in 1950, and finally Professor in 1954. Cohen was also the American Cancer Society Charles Hayden Professor of Biochemistry (1957–1971) and the Hartzell Professor of Therapeutic Research (1963–1971). In addition, he was Chairman of the Department of Therapeutic Research from 1963 to 1971. Cohen began working on bacterial viruses in 1945. His was the first systematic exploration of the biochemistry of virus-infected cells and of how viruses multiply. In 1953, he and Gerard R. Wyatt discovered that T-even phage DNA contains a unique pyrimidine base, 5-hydroxymethylcytosine, instead of the normal cytosine (3Wyatt G.R. Cohen S.S. The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine.Biochem J. 1953; 55: 774-782Crossref PubMed Scopus (223) Google Scholar). In the first JBC Classic reprinted here, Cohen and Joel G. Flaks describe the novel enzyme, deoxycytidylate hydroxymethylase, that converted dCMP to 5-hydroxymethyl-dCMP, which was ultimately converted to the triphosphate and incorporated into DNA. The enzyme was only found in E. coli cells infected with a T bacteriophage that contained 5-hydroxymethylcytosine in its DNA. In the second JBC Classic, Cohen and Hazel D. Barner present evidence that phage infection also stimulates the formation of a new form of thymidylate synthase, even though this enzyme was already known to exist in uninfected bacteria. Because Cohen had shown in his earlier work that T-even phage infection leads to a severalfold increase in the rate of DNA synthesis, this work suggested that the virus needed not only novel enzymes to produce the unique base but also needed to augment the activities of pre-existing enzymes to promote the big metabolic shift toward DNA synthesis. The discovery that virus infection creates new metabolic pathways and affects flux through existing pathways was of importance because it suggested that virus-specified enzymes could be used as biochemical targets for antiviral agents. In 1971, Cohen left the University of Pennsylvania for the University of Colorado in Denver. He then went to the State University of New York at Stony Brook in 1976, where he was named Distinguished Professor of Pharmacological Sciences and American Cancer Society Professor. In 1985, Cohen became Emeritus Professor of Pharmacological Sciences at the State University of New York at Stony Brook. He currently lives in Woods Hole, Massachusetts, where he is working on a text on polyamines and on a biography of the chemist, Thomas Cooper. Cohen received many awards and honors during his career including the Eli Lilly Award in bacteriology and immunology in 1951, the Mead Johnson Award given by the American Academy of Pediatrics in 1952, the Newcomb Cleveland Award of the American Association for the Advancement of Science in 1955, the French Society of Biological Chemists Medal in 1964, the Borden Award of the American Association of Medical Colleges in 1967, the Passano Award in 1974, and a medal from the Alumni Foundation of the City College of New York in 1978. He was also one of two scientists in the United States in 1957 to receive a lifetime grant from the American Cancer Society. Cohen served on the editorial boards of Virology, the Journal of Biological Chemistry, Bacteriological Reviews, and the Journal of Bacteriology. He is a member of the American Academy of Arts and Sciences (1963) and the National Academy of Sciences (1967) and served as president of the Society of General Physiologists in 1968.
Source: Journal of Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1541933589