个人简介

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

研究领域

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

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.

近期论文

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Closed for business: exit-channel coupling to active site conformation in bacterial RNA polymerase," Craig T. Martin & Karsten Theis, Nat Struct Mol Biol 21, 741?742, 2014. "Insights into the Mechanism of Initial Transcription in E coli RNA Polymerase. Energetic Mechanisms Leading to Initial Complex Instability and Abortive Cycling," Satamita Samanta & Craig T. Martin, J. Biol. Chem. 288, 31993-32003, 2013. "New Insights into the Mechanism of Initial Transcription: the T7 RNA Polymerase Mutant P266L Transitions to Elongation at Longer RNA Lengths than Wild Type," Luis Ramírez-Tapia & Craig T. Martin, J. Biol. Chem. 287, 37352-37361, 2012. "Direct Tests of the Energetic Basis of Abortive Cycling in Transcription," Ankit V. Vahia & Craig T. Martin, Biochemistry 50, 7015-7022, 2011. "Transcription Elongation Complex Stability: The Topological Lock," Xiaoqing Liu & Craig T. Martin, J. Biol. Chem. 284, 36262-36270, 2009. "Transcription: Initiation," Craig T. Martin & Olga S. Mironova, Wiley Encyclopedia of Chemical Biology, Vol 4 (Editor: Tadhg P. Begley), 584-595, 2009. "Dissociation of halted T7 RNA polymerase elongation complexes proceeds via a forward translocation mechanism," Yi Zhou, Deanna M. Navaroli, Metewo Selase Enuameh, & 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 and Craig T. Martin, J. Biol. Chem. 281, 24441-24448, 2006. "Mechanism of instability in abortive cycling by T7 RNA polymerase," Peng Gong and Craig T. Martin, J. Biol. Chem. 281, 23533-23544, 2006. "Light-Regulated Release of DNAand 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 (supplementary info available). See reports in NCI Nanotech News and Nature Materials "Stability of Gold Nanoparticle-Bound DNA toward Biological, Physical, and Chemical Agents," Gang Han, Craig T. Martin, and Vincent M. Rotello, Chem Biol Drug Des. 67 78-82, 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, and Vincent M. Rotello, Bioconjugate Chem. 16 1356-1359, 2005 "Structure and Function in Promoter Escape by T7 RNA Polymerase," Craig T. Martin, Edward A. Esposito, Karsten Theis, & Peng Gong, Prog Nucl Acids Res & Mol Biol, Kivie Moldave, Ed., 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 bubble collapse plays a key role in the transition to elongation in T7 RNA polymerase," Peng Gong, Edward A. Esposito and 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. "Evaluation of fluorescence spectroscopy methods for mapping melted regions of DNA along the transcription pathway," Craig T. Martin, Andrea Újvári, & Cuihua Liu, Methods Enzymol. 371, 13-33, 2003. "Binding of the Priming Nucleotide in the Initiation of Transcription by T7 RNA Polymerase," Iaroslav Kuzmine, Philip A. Gottlieb, & Craig T. Martin, J. Biol. Chem. 278, 2819-2823, 2003. "Promoter Clearance by T7 RNA Polymerase: Initial Bubble Collapse and Transcript Dissociation Monitored by Base Analog Fluorescence," Cuihua Liu & Craig T. Martin, J. Biol. Chem. 277, 2725-2731, 2002. Selected as a "Must Read" by Faculty of 1000! "Interrupting the Template Strand of the T7 Promoter Facilitates Translocation of the DNA During Initiation, Reducing Transcript Slippage and the Release of Abortive Products," Manli Jiang, Minqing Rong, Craig Martin, and William T. McAllister, J. Mol. Biol. 310, 509-522, 2001. "Inhibition of DNA transcription using cationic mixed monolayer protected gold clusters," Catherine M. McIntosh, Edward A. Esposito, III, Andrew K. Boal, Joseph M. Simard, Craig T. Martin, & Vincent M. Rotello, J. Am. Chem. Soc. 123, 7626-7629, 2001. "Structure in Nascent RNA Leads to Termination of Slippage Transcription by T7 RNA Polymerase," Iaroslav Kuzmine, Philip A. Gottlieb, & Craig T. Martin, Nucl. Acids Res. 29, 2601-2606, 2001. "Fluorescence Characterization of the Transcription Bubble in Elongation Complexes of T7 RNA Polymerase ," Cuihua Liu & Craig T. Martin, J. Mol. Biol. 308, 465-475, 2001. Reviewed in Current Opinions in Structural Biology & "Pre-steady State Kinetics of Initiation of Transcription by T7 RNA Polymerase - A New Kinetic Model ," Iaroslav Kuzmine & Craig T. Martin, J. Mol. Biol. 305, 559-566, 2001. "Evidence for DNA bending at the T7 RNA polymerase promoter," Andrea Újvári & Craig T. Martin, J. Mol. Biol. 295, 1173-84, 2000. "Identification of a Minimal Binding Element within the T7 RNA Polymerase Promoter," Andrea Újvári & Craig T. Martin, J. Mol. Biol. 273, 775-781, 1997. "Positioning of the Start Site in the Initiation of Transcription by T7 RNA Polymerase," Benjamin F. Weston, Iaroslav Kuzmine, & Craig T. Martin, J. Mol. Biol 272, 21-30, 1997. "Thermodynamic and Kinetic Measurements of Promoter Binding by T7 RNA Polymerase," Andrea Újvári & Craig T. Martin, Biochemistry 35, 14574-14582, 1996. "Major Groove Recognition Elements in the Middle of the T7 RNA Polymerase Promoter," Tong Li, Hoi Hung Ho, Maribeth Maslak, Charlie Schick & Craig T. Martin, Biochemistry 35, 3722-3727, 1996. "Identification of Essential Amino Acids Within the Proposed CuA Binding Site in Subunit II of Cytochrome c Oxidase," Henry Speno, M. Reza Taheri, Derek Sieburth, and Craig T. Martin, J. Biol. Chem. 270, 25363-25369, 1995. "Tests of a Model of Specific Contacts in T7 RNA Polymerase-Promoter Interactions," Charlie Schick and Craig T. Martin, Biochemistry 34, 666-672, 1995. "Effects of Solution Conditions on the Steady State Kinetics of Initiation of Transcription by T7 RNA Polymerase," Maribeth Maslak and Craig T. Martin, Biochemistry, 33, 6918-6924, 1994. "Kinetic Analysis of T7 RNA Polymerase Transcription Initiation From Promoters Containing Single Stranded Regions," Maribeth Maslak and Craig T. Martin, Biochemistry 32, 4281-4285, 1993. "Identification of Specific Contacts in T3 RNA Polymerase-Promoter Interactions: Kinetic Analysis using Small Synthetic Promoters," Charlie Schick and Craig T. Martin, Biochemistry 32, 4275-4280, 1993. "Tests of a Model for Promoter Recognition by T7 RNA Polymerase: Thymine Methyl Group Contacts," Maribeth Maslak, Martha D. Jaworski, and Craig T. Martin, Biochemistry 32, 4270-4274, 1993. "Reaction of Single-Stranded DNA with Hydroxyl Radical Generated by Iron(II)-Ethylenediaminetetraacetic Acid," Richard V. Prigodich & Craig T. Martin, Biochemistry 29, 8017-8019, 1990. "T7 RNA Polymerase Interacts with Its Promoter from One Side of the DNA Helix," Daniel K. Muller, Craig T. Martin, and Joseph E. Coleman, Biochemistry 28, 3306-3313, 1989. "T7 RNA Polymerase Does Not Interact with the 5'-Phosphate of the Initiating Nucleotide," Craig T. Martin and Joseph E. Coleman, Biochemistry 28, 2760-2762, 1989. "Processivity of Proteolytically Modified Forms of T7 RNA Polymerase," Daniel K. Muller, Craig T. Martin, and Joseph E. Coleman, Biochemistry 27, 5763-5771, 1988. "Processivity in Early Stages of Transcription by T7 RNA Polymerase," Craig T. Martin, Daniel K. Muller, and Joseph E. Coleman, Biochemistry 27, 3966-3974, 1988. "On the Nature of Cysteine Coordination to CuA in Cytochrome c Oxidase," Craig T. Martin, Charles P. Scholes, and Sunney I. Chan, J. Biol. Chem. 263, 8420-8429, 1988. "A Proposal for the Site and Mechanism of Redox-Linked Proton Translocation in Cytochrome c Oxidase," Sunney I. Chan, Peter Mark Li, Thomas Nilsson, Jeff Gelles, David F. Blair, and Craig T. Martin, Prog. Clin. Biol. Res. 274, 731-747, 1988. "Kinetic Analysis of T7 RNA Polymerase-Promoter Interactions with Small Synthetic Promoters," Craig T. Martin and Joseph E. Coleman, Biochemistry 26, 2690-2696, 1987. "Zinc Metalloproteins Involved in Replication and Transcription," David P. Giedroc, Kathleen M. Keating, Craig T. Martin, Kenneth R. Williams, and Joseph E. Coleman, J. Inorg. Biochem. 28, 155-169, 1986. "Transcription by T7 RNA Polymerase Is Not Zinc-Dependent and Is Abolished on Amidomethylation of Cysteine-347", Garry C. King, Craig T. Martin, Thang T. Pham, and Joseph E. Coleman, Biochemistry 25, 36-40, 1986. "The Identification of Histidine Ligand(s) to Cytochrome a in Cytochrome c Oxidase," Craig T. Martin, Charles P. Scholes, and Sunney I. Chan, J. Biol. Chem. 260, 2857-2861, 1985. "The Metal Centers of Cytochrome c Oxidase: Structure and Function," Sunney I. Chan, Craig T. Martin, Hsin Wang, David F. Blair, Jeff Gelles, Gary W. Brudvig, and Tom H. Stevens, in Biochemical and Biophysical Studies of Proteins and Nucleic Acids, Tung-Bin Lo, Teh-Yung Liu, and Choh-Hao Li, eds., Elsevier, New York, 219-239, 1984. "Energetics and Molecular Dynamics of the Proton Pumping Photocycle in Bacteriorhodopsin," Robert R. Birge, Albert F. Lawrence, Thomas M. Cooper, Craig T. Martin, David F. Blair, and Sunney I. Chan, in Nonlinear Electrodynamics in Biological Systems, W. Ross Adey and Albert F. Lawrence, eds., Plenum, New York, 107-120, 1984. "Structural Studies on the Metal Centers of Cytochrome c Oxidase," Jeff Gelles, David F. Blair, Craig T. Martin, Hsin Wang, and Sunney I. Chan, in Frontiers in Biochemical and Biophysical Studies of Proteins and Membranes, Teh-Yung Liu, Shunpei Sakakibara, Alan N. Schechter, Kunio Yagi, Haruaki Yajima, and Kerry T. Yasunobu, eds., Elsevier, New York, 259-277, 1983. "The Structure of the Metal Centers in Cytochrome c Oxidase," Sunney I. Chan, Craig T. Martin, Hsin Wang, Gary W. Brudvig, and Tom H. Stevens, in The Coordination Chemistry of Metalloenzymes, I. Bertini, R. S. Drago, and C. Luchinat, eds., D. Reidel Pub. Co., Boston, 313-328, 1983. "A Resonance Raman Investigation of Perturbed States of Tree and Fungal Laccase," D. F. Blair, G. W. Campbell, V. Lum, C. T. Martin, H. B. Gray, B. G. Malmström, and Sunney I. Chan, J. Inorg. Biochem. 19, 65-73, 1983. "The Metal Centers of Cytochrome c Oxidase: Structures and Interactions," David F. Blair, Craig T. Martin, Jeff Gelles, Hsin Wang, Gary W. Brudvig, Tom H. Stevens, and Sunney I. Chan, Chemica Scripta 21, 43-53, 1983. "The Nature and Distribution of the Metal Centers in Cytochrome c Oxidase," Sunney I. Chan, Gary W. Brudvig, Craig T. Martin, and Tom H. Stevens, in Electron Transport and Oxygen Utilization, Chien Ho, ed., Elsevier, Amsterdam, 171-177, 1982. "The Nature of CuA in Cytochrome c Oxidase," Tom H. Stevens, Craig T. Martin, Hsin Wang, Gary W. Brudvig, Charles P. Scholes, and Sunney I. Chan, J. Biol. Chem. 257, 12106-12113, 1982. "Reactions of Nitric Oxide with Tree and Fungal Laccase," Craig T. Martin, Randall H. Morse, Robert M. Kanne, Harry B. Gray, Bo G. Malmström, and Sunney I. Chan, Biochemistry 20, 5147-5155, 1981.