Processive Degradation and Eukaryotic Recombination: the Work of Maxine Singer
Year: 2007
Type: article
Abstract: The Processive Degradation of Individual Polyribonucleotide Chains. I. Escherichia coli Ribonuclease II (Nossal, N. G., and Singer, M. F. (1968) J. Biol. Chem. 243, 913–922) The Processive Degradation of Individual Polyribonucleotide Chains. II. Micrococcus lysodeikticus Polynucleotide Phosphorylase (Klee, C. B. and Singer, M. F. (1968) J. Biol. Chem. 243, 923–927) Structure of Simian Virus 40 Recombinants That Contain Both Host and Viral DNA Sequences. I. The Structure of Variant CVPS/1/P2 (EcoRI res) (Wakamiya, T., McCutchan, T., Rosenberg, M., and Singer, M. (1979) J. Biol. Chem. 254, 3584–3591) Maxine Frank Singer was born in 1931 in New York City. She received her A.B. from Swarthmore College in Pennsylvania in 1952 and her Ph.D. in biochemistry from Yale University in 1957. After graduating, Singer became a postdoctoral fellow in Leon Heppel's laboratory at the National Institute for Arthritis and Metabolic Diseases (NIAMD) in Bethesda, Maryland. At this time, Heppel's research focused on polynucleotide phosphorylase (PNPase), an enzyme discovered by Journal of Biological Chemistry (JBC) Classics author Severo Ochoa (1Salas M. Smith M.A. Stanley Jr., W.M. Wahba A.J. Ochoa S. JBC Classics.J. Biol. Chem. 1965; 240: 3988-3995http://www.jbc.org/cgi/content/full/281/21/e16Abstract Full Text PDF PubMed Google Scholar), that converts ADP and other nucleoside diphosphates into RNA-like (NMP)n polymers. As reported in a previous JBC Classic, Heppel and Singer looked at the mechanisms of the PNPase polymerization reaction as well as the reverse reaction, the phosphorolysis of the polymers (2Singer M.F. Heppel L.A. Hilmoe R.J. JBC Classics.J. Biol. Chem. 1960; 235: 738-750Abstract Full Text PDF PubMed Google ScholarSinger M.F. Hilmoe R.J. Heppel L.A. J. Biol. Chem. 1960; 235: 751-757Abstract Full Text PDF PubMed Google ScholarWeiner J.H. Heppel L.A. J. Biol. Chem. 1971; 246: 6933-6941http://www.jbc.org/cgi/content/full/281/18/e13Abstract Full Text PDF Google Scholar). In 1958 Singer received a research staff appointment in the section on Enzymes and Cellular Biochemistry at NIAMD. She continued to study ribonucleotide degradation, as reported in the first two JBC Classics reprinted here. In the first JBC Classic, Singer and Nancy Nossal show that enzymatic degradation by Escherichia coli ribonuclease II starts at the 3′-hydroxyl end. Furthermore, they demonstrate that the enzyme hydrolyzes a given polyribonucleotide chain to completion before releasing a small oliogonucleotide and initiating hydrolysis of a new chain. Singer termed this “processive degradation.” In the second JBC Classic, which was printed back-to-back with the first, Singer and Claude Klee describe similar experiments with PNPase from Micrococcus lysodeikticus and show that this enzyme also degrades polyribonucleotide chains to completion before releasing the end product and starting degradation of another chain. The paper also discusses several ways in which an enzyme might hang on to a growing polymer, such as threading the polymer through a hole or depression in the enzyme. These two JBC Classic papers were the first demonstrations of processive reactions. In the final JBC Classic, Singer changes the focus of her research to recombination in eukaryotic cells. She and her colleagues present the nucleotide sequence of a defective variant of simian virus 40 and show that the variant contains several large deletions, an inversion, and several DNA sequences derived from the permissive monkey cells in which the virus was propagated. From their data, they surmise that the recombinational events that resulted in the formation of the variant did not depend on extensive homology between recombining segments. In a paper that accompanied this Classic (3McCutchan T. Singer M. Rosenberg M. Structure of simian virus 40 recombinants that contain both host and viral DNA sequences. II. The structure of variant 1103 and its comparison to variant CVPS/1P2 (EcoRI res).J. Biol. Chem. 1979; 254: 3592-3597Abstract Full Text PDF PubMed Google Scholar), Singer and her colleagues present the primary structure of another defective variant and compare it with the one presented here. In 1974, Singer became chief of the Section of Nucleic Acid Enzymology, Division of Cancer Biology and Diagnosis (DCBD) at the National Cancer Institute, and in 1980 she became chief of the DCBD's Laboratory of Biochemistry. She held this position until 1988, when she became president of the Carnegie Institution in Washington, D. C. Singer remains at the Carnegie Institution today and also retains her association with the National Cancer Institute as Scientist Emeritus. In addition to her laboratory research, Singer has devoted considerable time and energy to other scientific and professional pursuits. She and Dieter Söll co-chaired the 1973 Gordon Conference on Nucleic Acids in which early concerns about risks in recombinant DNA research were raised. Singer was an organizer of the famous 1975 Asilomar Conference on Recombinant DNA and was one of five signers of the summary statement of the Asilomar report, which drew up guidelines for recombinant DNA research. Singer has been a member of the Board of Governors and Scientific Advisory Council for the Weizmann Institute of Science since 1978 and was chairwoman of the editorial board for the Proceedings of the National Academy of Sciences from 1985 to 1988. She was elected to the National Academy of Sciences in 1979 and to membership in the Pontifical Academy of Sciences in 1986. Her many awards include the Washington Academy of Science Award for Achievement in Biological Science (1969), the National Institutes of Health Director's Award (1977), the American Association of Applied Sciences Science, the Freedom and Responsibility Award (1982), the Department of Health and Human Services Distinguished Service Medal (1983), the Presidential Distinguished Executive Rank Award (1987), the United States Distinguished Executive Rank Award (1987), the National Medal of Science (1992), and the National Academy of Sciences Public Welfare Medal (2007).
Source: Journal of Biological Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1529707868