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Myron F. Goodman

Professor of Molecular Biology and Chemistry
Molecular Biology

Ph.D., 1968, John Hopkins University
B.S.E.E., 1962, Columbia University
B.S., 1960, Queens College
Office: RRI 119C
Phone: (213) 740-5190
Fax: (213) 740-8631
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Research Focus

Biochemical Mechanisms of Mutagenesis and DNA Repair

Our primary research goal is to understand the molecular basis of mutagenesis. There are 3 projects under investigation. The first is to study biochemical and physical-chemical mechanisms governing DNA replication fidelity. DNA polymerases make mistakes at rates as often as one in a thousand to as little as one in a million, depending on the type of error, surrounding DNA sequence, and on the properties of the enzyme. We have developed a simple polyacrylamide gel electrophoresis assay to measure DNA synthesis fidelity at any DNA template site, and we are analyzing how fidelity depends on DNA polymerases, DNA sequences, and on protein components of the replication complex.

When DNA is heavily damaged following exposure of a cell to chemical mutagens or UV light, more than 20 genes in the SOS regulon of E. coli are induced, allowing the cell to copy past nonrepairable DNA lesions resulting in a high frequency of mutations. The second project is to investigate the biochemical basis of SOS-induced error prone repair in E. coli. We discovered that E. coli DNA polymerase II was induced as part of the SOS regulon and have identified and cloned the structural gene for pol II, the damage inducible dinA gene. Genetic and biochemical studies are currently underway to investigate the role of pol II in vivo and to study its properties in vitro.

Are DNA repair enzymes induced in non-dividing eucaryotic cells? The third project is to identify and study normal and damage-induced DNA replication, repair, and nucleotide metabolisms enzymes using neuron and astrocyte primary and transformed cell cultures.

Selected publications

1. Petruska, J., Arnheim, N., and Goodman, M. F. Stability of intrastrand hairpin structures formed by the CAG/CTG class of DNA triplet repeats associated with neurological diseases. Nucleic Acids Res. 24, 1992-1998 (1996).
2. Bloom, L. B., Chen, X., Kuchnir Fygenson, D., Turner, J., O'Donnell, M., and Goodman, M. F. Fidelity of Escherichia coli DNA Polymerase III Holoenzyme: The Effects of bets, gamma Complex Processivity Proteins and epsilon Proofreading Exonuclease on Nucleotide Misincorporation Efficiencies. J. Biol. Chem. 272, 27919-27930 (1997).
3. Goodman, M. F. Hydrogen bonding revisited: geometric selection as a principal determinant of DNA replication fidelity. Proc. Natl. Acad. Sci. USA 94, 10493-10495 (1997).
4. Goodman, Myron F. and Fygenson, D. F. DNA Polymerase Fidelity: From Genetics Toward a Biochemical Understanding. Genetics 148, 1475-1482 (1998).
5. Tang, M. Bruck, I., Eritja, R., Turner, J., Frank, E. G., Woodgate, R., O'Donnell, M., and Goodman, M. F. Biochemical Basis of SOS-Induced Mutagenesis in Escherichia coli: Reconstitution of in vitro lesion bypass dependent on the UmuD'2C Mutagenic Complex and RecA Protein. Proc. Natl. Acad. Sci. USA 95, 9755-9760 (1998).
6. Goodman, M. F. Purposeful Mutations. Nature 395, 221-223 (1998).
7. Bertram, J. G., Bloom, L. B., Turner, J., O'Donnell, M., Beechem, J. M., and Goodman, M. F. Pre-steady State Analysis of the Assembly of Wild Type and Mutant Circular Clamps of Escherichia coli DNA Polymerase III onto DNA. J. Biol. Chem. 273, 24564-24574 (1998).
8. Goodman, M. F. On the wagon: DNA polymerase joins H-bonds anonymous. Nature Biotechnology 17, 640-641 (1999).
9. Tang, M., Shen, X., Frank, E. G., O'Donnell, M., Woodgate, R., and Goodman, M. F. UmuD'2C is an error-prone DNA polymerase, Escherichia coli pol V. Proc. Natl. Acad. Sci. USA 96, 8919-8924 (1999).
10. Rangarajan, S., Woodgate, R., and Goodman, M. F. A Phenotype For Enigmatic DNA Polymerase II: A Pivotal Role For Pol II In Replication Restart In UV-irradiated Escherichia coli. Proc. Natl. Acad. Sci. USA 96, 9224-9229 (1999).


Chemistry Dept., USC College of Letters, Arts & Sciences