Education:
BS 1961 - Queens College
BS 1966 Electrical Engineering - Columbia University
PhD 1968 Electrical Engineering - Johns Hopkins University
Postdoctoral Research Fellowship:
1968 - 1973 Johns Hopkins University, Balitmore, Maryland
Started at USC: 1973
Research Topics: DNA & RNA, Structural Biology
Research Description
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.
10 Selected Publications:
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Madia F,Wei M,Yuan V,Hu J,Gattazzo C,Pham P,Goodman MF,Longo VD - Oncogene homologue Sch9 promotes age-dependent mutations by a superoxide and Rev1/Pol{zeta}-dependent mechanism. - J Cell Biol [2009] Aug 17;(): PubMed
Chelico L,Pham P,Petruska J,Goodman MF - Biochemical basis of immunological and retroviral responses to DNA-targeted cytosine deamination by AID and APOBEC3G. - J Biol Chem [2009] Aug 13;(): PubMed
Jiang Q,Karata K,Woodgate R,Cox MM,Goodman MF - The active form of DNA polymerase V is UmuD'2C-RecA-ATP. - Nature [2009] Jul 16;460(7253):359-63 PubMed
Maccarthy T,Kalis SL,Roa S,Pham P,Goodman MF,Scharff MD,Bergman A - V-region mutation in vitro, in vivo, and in silico reveal the importance of the enzymatic properties of AID and the sequence environment. - Proc Natl Acad Sci U S A [2009] May 14;(): PubMed
Chelico L,Pham P,Goodman MF - Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA. - Nat Struct Mol Biol [2009] May;16(5):454-5; author reply 455-6 PubMed
Kamerlin SC,McKenna C,Goodman MF,Warshel A - A Computational Study of the Hydrolysis of dGTP Analogues with Halomethylene Modified Leaving Groups in Solution: Implications for the Mechanism of DNA Polymerases. - Biochemistry [2009] Apr 24;(): PubMed
Upton TG,Kashemirov BA,McKenna CE,Goodman MF,Prakash GK,Kultyshev R,Batra VK,Shock DD,Pedersen LC,Beard WA,Wilson SH - alpha,beta-Difluoromethylene Deoxynucleoside 5'-Triphosphates: A Convenient Synthesis of Useful Probes for DNA Polymerase beta Structure and Function. - Org Lett [2009] Apr 7;(): PubMed
Indiani C,Langston LD,Yurieva O,Goodman MF,O'Donnell M - Inaugural Article: Translesion DNA polymerases remodel the replisome and alter the speed of the replicative helicase. - Proc Natl Acad Sci U S A [2009] Mar 11;(): PubMed
Rausch JW,Chelico L,Goodman MF,Le Grice SF - Dissecting APOBEC3G substrate specificity by nucleoside analog interference. - J Biol Chem [2009] Jan 9;(): PubMed
Chelico L,Pham P,Goodman MF - Stochastic properties of processive cytidine DNA deaminases AID and APOBEC3G. - Philos Trans R Soc Lond B Biol Sci [2009] Mar 12;364(1517):583-93 PubMed
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