Zvi Kelman
Assistant Professor

University of Maryland Biotechnology Institute
Center for Advanced Research in Biotechnology
9600 Gudelsky Drive
Rockville, MD 20850

Phone:  (301) 738-6294
Fax: (301) 738-6255
Email:  kelman@carb.nist.gov
 
 Ph.D. - Biochemistry and Molecular Biology, Cornell University Medical School, 1996.

Research: Biochemistry of DNA Replication

Research interests in our laboratory focus on understanding the mechanism of chromosomal DNA replication. We are studying the replication machinery of the archaeaon Methanobacterium thermoautotrophicum (Mth) as a model for eukaryotes. Both the initiation and elongation phases of the replication process are currently being investigated using a range of biochemical and molecular biological approaches. The events leading to the initiation of chromosomal DNA replication are well understood in bacteria. In eukaryotes, genetic studies identified many of the proteins needed for the initiation phase, but little is known about their function or biochemical properties. The Mth origin of replication and homologues of the eukaryotic initiation proteins (including the helicase, MCM and the initiation protein, Cdc6) have been identified and purified. We are currently in the process of biochemically characterizing these factors. The other project involves the study of the elongation phase of DNA replication. The Mth proteins needed for DNA synthesis and for Okazaki fragment maturation have been cloned and purified. These include the three polymerases and their accessory factors, the single stranded DNA binding protein, DNA primase, and DNA ligase. The biochemical properties of these enzymes are currently being studied. Taken together, these studies will shed light on the replication machinery in the more complex, but homologous, eukaryotic system. A deep understanding of the mechanisms by which DNA replication is initiated and controlled are of great importance, and their elucidation will contribute to our understanding of the etiology of cancer and other diseases.

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