Professor
B.A., Univ. California/San Diego; Ph.D. 1984, California Institute of Technology; NIH Postdoctoral Fellowship, 1985-1988, Yale Univ.

Biochemistry
Enzymology of transcription; structure and function in enzyme-DNA interactions; kinetics and thermodynamics; nucleotide analogs, SELEX, fluorescence spectroscopy.

Department of Chemistry, 701A LGRT
University of Massachusetts
710 North Pleasant Street
Amherst, MA 01003-9336

office: 403D LGRT Tower A
tel: 413-545-3299 fax: 413-545-4490

cmartin@chem.umass.edu

Martin Research Group

Principal Research Interests

My group is interested in understanding specific chemical interactions which underlie complex enzyme systems. A major focus of the lab is to understand structure and function in enzyme-nucleic acid interactions. In transcription, the enzyme RNA polymerase must not only bind specifically to its promoter DNA sequence but must then initiate the processive catalysis of template-dependent RNA synthesis, leave the initial recognition site (promoter), and continue on to a stable, sequence-independent complex.

The T7 family of RNA polymerases present an ideal model system for the study of transcription. The single subunit enzyme is relatively simple and can be readily purified in large quantities from overproducing strains of E. coli. The chemical synthesis of oligonucleotides containing specifically modified base substituents, has allowed us to map out functional groups on the DNA which are critical to recognition and initiation. We can, for example, remove a single hydrogen bond donor or acceptor from a known position in the DNA helix and then ask quantitatively how recognition is perturbed. We can also introduce fluorescent base analogs that report on the melted state of the DNA, in order to map movement of the transcription bubble.

Recent crystal structures of initiation and elongation complexes (with DNA and RNA) provide a wealth of testable models for various aspects of this complex chemical process. Stopped flow and quench flow kinetic studies have allowed a dissection of the mechanistic steps in the initiation of transcription, while site-directed mutagenesis has allowed us to probe possible structural interactions. Our ultimate goal is to directly link changing structural interactions between the enzyme and DNA to individual chemical events in the transcription process.

“Dissociation of halted T7 RNA polymerase elongation complexes proceeds via a forward translocation mechanism,” Yi Zhou & Craig T. Martin, Proc. Natl. Acad. Sci., U.S.A., 104, 10352-10357, 2007.

“Twisted or shifted? Fluorescence measurements of late intermediates in transcription initiation by T7 RNA polymerase,” Rosemary S. Turingan, Karsten Theis & Craig T. Martin, Biochemistry, 46, 6165-6168, 2007.

“Structural Confirmation of a Bent and Open Model for the Initiation Complex of T7 RNA Polymerase,” Rosemary S. Turingan, Cuihua Liu, Mary E. Hawkins, & Craig T. Martin, Biochemistry, 46, 1714-1723, 2007.

“Observed instability of T7 RNA polymerase elongation complexes can be dominated by collision-induced ‘bumping’,” Yi Zhou & Craig T. Martin, J. Biol. Chem. 281, 24441-24448, 2006.

“Mechanism of instability in abortive cycling by T7 RNA polymerase,” Peng Gong & Craig T. Martin, J. Biol. Chem. 281, 23533-23544, 2006.

“Light-Regulated Release of DNA and Its Delivery to Nuclei by Means of Photolabile Gold Nanoparticles,” Gang Han, Chang-Cheng You, Byoung-jin Kim, Rosemary S. Turingan, Neil S. Forbes, Craig T. Martin, & Vincent M. Rotello, Angew. Chem. Int. Ed. 45, 3165-3169, 2006.

“Stability of Gold Nanoparticle-Bound DNA toward Biological, Physical, and Chemical Agents,” Gang Han, Craig T. Martin, & Vincent M. Rotello, Chem Biol Drug Des 1, 1-5, 2005.

“Controlled Recovery of the Transcription of Nanoparticle-Bound DNA by Intracellular Concentrations of Glutathione,” Gang Han, Nandini S. Chari, Ayush Verma, Rui Hong, Craig T. Martin, & Vincent Rotello, Bioconjugate Chemistry, 16, 1356-1359, 2005.

"Structure and Function in Promter Escape by T7 RNA," Craig T. Martin, Edward A. Esposito, Karsten Theis & Peng Gong, Progress in Nucleic Acid Research and Molecular Biology 80, 323-347, 2005.

"Topological and conformational analysis of the initiation and elongation complex of T7 RNA polymerase suggests a new twist," Karsten Theis, Peng Gong and Craig T. Martin, Biochemistry 43, 12709-12715, 2004.

“Initial DNA bubble collapse plays a key role in the transition to elongation in T7 RNA polymerase,” Peng Gong, Edward A. Esposito, & Craig T. Martin, J. Biol. Chem. 279, 44277-44285, 2004.

"Crosslinking of Promoter DNA to T7 RNA Polymerase Does Not Prevent Formation of a Stable Elongation Complex," Edward A. Esposito and Craig T. Martin, J. Biol. Chem. 279, 44270-44276,2004.

Click Here for a complete list of publications.