Department of Biochemistry
School of Medicine & Biomedical Sciences
Faculty
MARK D. SUTTON, Ph.D.
Associate Professor
Regulation and Coordination of DNA Replication and DNA Repair
Chromosomal DNA replication is a highly regulated event that is tightly coupled to cell growth. This event requires the concerted actions of numerous proteins and can be divided into three distinct stages referred to as initiation, elongation, and termination of DNA replication. In addition to DNA replication, a variety of DNA repair pathways exist. The combination of accurate replication and efficient repair are crucial for maintaining the integrity of an organism's genetic material. Research in my lab is directed at understanding the mechanisms of, regulation of, and coordination of DNA replication and repair. We are particularly interested in the roles played in these processes by molecular machines.
My lab utilizes a combination of biochemical and genetic approaches to investigate the molecular mechanisms of DNA replication and DNA repair in Escherichia coli. We are currently concentrating our research efforts in two related areas. First, we are investigating the molecular mechanism of translesion DNA synthesis, the potentially mutagenic replication over lesions in the DNA. In E. coli, translesion DNA synthesis depends on the umuDC-encoded DNA polymerase V (Pol V), acting together with other cellular proteins as a molecular machine. In vitro, Pol V-dependent translesion DNA synthesis is stimulated by the b clamp and clamp loader complex of another molecular machine, the replicative DNA polymerase, DNA Pol III. The b clamp functions as a ring-shaped dimer that is loaded onto DNA by the clamp loader complex. Once loaded, the b clamp slides freely along the DNA. We are interested in understanding how specific interactions of both Pol III and Pol V with the b clamp help coordinate the actions of these two molecular machines to enable translesion DNA synthesis.
The second main area of our research involves investigation into how the b clamp coordinates initiation of DNA replication with elongation and certain DNA repair pathways. b interacts with proteins involved in each of these three events. We are interested in characterizing these various protein-protein interactions as part of our larger effort to understand how an organism coordinates DNA replication with repair. Two genetic selections we developed have resulted in identification of a collection of novel mutant b clamp proteins. Our ongoing structure-function studies of these mutant b clamps are providing insights into how b coordinates the actions of the molecular machines involved in DNA replication and repair.
Selected Recent Publications
Sutton, M.D., Damage Signals triggering the E. coli SOS response. In: W. Siede, Y.W. Kow, and P.W. Doetsch (Eds.) DNA Damage Recognition. Marcel-Decker, Inc. New York, NY. (Book Chapter). In Press.
Duzen, J.M., Walker, G.C. and Sutton, M.D. (2004) Identification of specific amino acid residues in the E. coli ß processivity clamp involved in interactions with DNA polymerase III, UmuD and UmuD'. DNA Repair 3: 301-312.
Sutton, M. D., Narumi, I., and Walker, G. C. (2002) Posttranslational Modification of the umuD-Encoded Subunit of Escherichia coli DNA Polymerase V Regulates its Interactions with the beta Processivity Clamp. Proc. Natl. Acad. Sci. U.S.A. 99: 5307-5312.
Sutton, M. D., Guzzo, A., Narumi, I., Costanzo, M., Altenbach, C., Ferentz, A. E., Hubbell, W., and Walker, G. C. (2002) A Model for the Structure of the Escherichia coli SOS-Regulated UmuD2 Protein. DNA Repair 1: 77-93.
Sutton, M. D. and Walker, G. C. (2001) Managing DNA Polymerases: Coordinating DNA Replication, DNA Repair, and DNA Recombination. Proc. Natl. Acad. Sci. U.S.A. 98: 8342-8349.
Sutton, M. D., Farrow, M., Burton, B., and Walker, G. C. (2001). Genetic Interactions Between the Escherichia coli umuDC Gene Products and the b Processivity Clamp of the Replicative DNA Polymerase. Journal of Bacteriology 183:2897-2909.
Sutton, M. D. and Walker, G. C. (2001). umuDC-Mediated Cold Sensitivity is a Manifestation of Functions of the UmuD²C Complex Involved in a DNA Damage Checkpoint Control. Journal of Bacteriology 183:1215-1224.
Sutton, M. D., Murli, S., Opperman, T., Klein, C., and Walker, G. C. (2001). umuDC-dnaQ Interaction and Its Implications for Cell Cycle Regulation and SOS Mutagenesis in Escherichia coli. Journal of Bacteriology 183:1085-1089.
Sutton M. D., Smith, B. T., Godoy, V. G., and Walker, G. C. (2000). The SOS Response: Recent Insights into umuDC-Dependent Mutagenesis and DNA Damage Tolerance. Annual Review of Genetics 34:479-497.
Sutton, M. D., Opperman, T., and Walker, G. C. (1999). The Escherichia coli SOS Mutagenesis Proteins UmuD and UmuD' Interact Physically With the Replicative DNA Polymerase. Proc. Natl. Acad. Sci. U.S.A. 96:12373-12378.
Sutton, M. D., Carr, K. M., Vicente, M., and Kaguni, J. M. (1998). Escherichia coli DnaA Protein: The N-Terminal Domain and Loading of DnaB Helicase at the E. coli Chromosomal Origin. Journal of Biological Chemistry 273:34255-34262.
Return
to Faculty Page
BCH Home
UB Home