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The People of Tulane Cancer Center Research


Jim D KaramJim D. Karam, Ph.D.
Professor and Chairman of Biochemistry
Tulane Cancer Center Contributing Member

Contact Information
Email: karamoff@tulane.edu
Phone: 504-988-1995
Address: 1430 Tulane Ave., Box SL-43, New Orleans, LA 70112-2699
Karam web Site


Biographical Narrative

Dr. Karam received his B.S. in Biology/Chemistry from the American University of Beirut, Lebanon in 1958. He carried out his doctoral studies in Biochemistry with Dr. Edward Glassman at the University of North Carolina, Chapel Hill, receiving his Ph.D. in 1965. His postdoctoral studies were carried out with Dr. Joseph F. Speyer at the Cold Spring Harbor Laboratory in New York. In 1967 he became Research Assistant Professor of Genetics and Cell Biology at the University of Connecticut at Storrs and in 1968 moved to Sloan-Kettering Institute for Cancer Research in New York City as a Research Associate. In 1971 Dr. Karam joined the faculty at the Medical University of South Carolina where he attained the rank of professor. He was appointed to his current position as Professor and Chair of the Department of Biochemistry in the School of Medicine at Tulane University Health Sciences Center in November, 1991. The primary focus of Dr. Karam's research is on the genetic and biochemical mechanisms that regulate the multiprotein DNA replication machine (DNA replisome) of bacteriophage T4 and the T4-related phages. These bacterial viruses encode all of the proteins required for assembly of the viral replisome and replication of the ~170,000 base-pair (bp) linear and circularly permuted DNA genome. Complexity of the T4 replisome resembles that of many large pathogenic DNA viruses, like the herpes, vaccinia, and adeno viral groups At the core of the T4 DNA replisome is the replicative DNA polymerase, product of phage gene 43 (gp43), which works in a complex with a large number of other proteins to affect rapid and accurate genome replication in the phage-infected Escherichia coli host. T4 gp43 carries several functions in its single polypeptide chain, including two catalytic activities that work together to control fidelity of replicative DNA synthesis. These two activities are the polymerase (DNA synthesizing) activity, which determines fidelity of nucleotide base selection and rate of DNA chain extension, and the editing or proofreading (3'-exonuclease) activity, which removes misincorporated bases. Studies in Dr. Karam's laboratory are determining how these two activities of the enzyme are coordinated to maintain low mutation rates. Other studies are addressing relationships between two types of nucleic-acid binding functions of this DNA polymerase. The nucleotide-sequence independent DNA binding activity used for phage DNA replication and a highly specific RNA binding activity through which the enzyme binds its own mRNA and regulates its own biosynthesis at the level of translation are both being studied. Recent results suggest that this viral enzyme uses RNA as a scaffold to build the multiprotein replisome. Experimental tools are being generated to find out if cellular and other viral DNA polymerases also use specific RNA to initiate replisome assembly.

Selected Publications
Wang J., Sattar AK, Wang CC, Karam JD, Konigsberg WH, Steitz TA. Crystal structure of a pol alpha family replication DNA polymerase from bacteriophage RB69. Cell 89: 1087-1099 (1997)

Dressman HK, Wang CC, Karam JD and Drake JW. Retention of replication fidelity by a DNA polymerase functioning in a distantly related environment. Proc Natl Acad Sci USA 94: 8042-8046 (1997

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Yeh LS, T. Hsu and Karam JD. Divergence of a DNA replication gene cluster in the T4-related bacteriophage RB69. J Bacteriol 180: 2005-2013 (1998)

Yang G, Lin T, Karam JD, Konigsberg WH.Steady-state kinetic characterization of RB69 DNA polymerase mutants that affect dNTP incorporation. Biochemistry 38: 8094-8101 (1999)

Pavlov AR, Karam JD. Nucleotide-sequence-specific and non-specific interactions of T4 DNA polymerase with its own mRNA. Nucleic Acids Res 28: 4657-4664 (2000)

Bebenek A, Dressman HK, Carver GT, Ng S, Petrov V, Yang G, Konigsberg WH, Karam JD, Drake JW. Interacting fidelity defects in the replicative DNA polymerase of bacteriophage RB69. J Biol Chem 276: 10387-10397 (2001)

 

1430 Tulane Ave, New Orleans, LA 70112 504-988-5263 medsch@tulane.edu