University at Buffalo
The Witebsky Center

The Witebsky Center
University at Buffalo
Bacteriology Host-Microbe Interactions Immunology Parasitology Virology
The Witebsky Center The Witebsky Center
Mark D. Sutton

Mark D. Sutton, Ph.D.,
Professor
Department of Biochemistry
Phone: (716) 829-3581
Fax: (716) 829-2661
Email: mdsutton@buffalo.edu

 

sutton

Mechanisms underlying clonal expansion and pathoadaptation in Pseudomonas aeruginosa. Pseudomonas aeruginosa is a gram-negative human opportunistic pathogen that chronically infects immunocompromised individuals, and is the leading cause of morbidity and mortality for Cystic Fibrosis (CF) patients. CF is an inherited, chronic disease affecting primarily the lungs and digestive system. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the lungs, mutations in CFTR lead to the accumulation of thick mucous, which predisposes these individuals to P. aeruginosa infections. One remarkable feature of P. aeruginosa is its ability to undergo clonal expansion during chronic infection. Clonal expansion refers to the process by which a population of P. aeruginosa cells undergoes continual selection for the accumulation of specific genetic changes that collectively promote its long-term survival and enhance pathogenesis. We are interested in understanding the mechanisms that contribute to DNA mutagenesis in P. aeruginosa, and are particularly interested in determining the contribution of these mechanisms to clonal expansion and pathoadaptation. Current efforts are focused on determining the roles of mismatch repair, base excision repair, and error-prone DNA polymerases in spontaneous and DNA damage-induced mutagenesis.

Regulation and coordination of DNA replication, DNA repair and DNA damage tolerance in Escherichia coli. Genomic integrity depends upon not only high fidelity DNA replication, but also on a variety of highly accurate DNA repair processes, as well as DNA damage tolerance mechanisms that act to catalyze replication over DNA lesions that cannot be repaired. We are interested in developing an integrated mechanistic view of how organisms coordinate the actions of their replication machinery with those of other cellular factors involved in DNA repair and damage tolerance. Work from our laboratory and others have demonstrated unambiguously that DNA polymerase processivity clamps (beta or DnaN sliding clamps) play critically important roles in this complex process. Current efforts are focused on understanding the roles of the E. coli beta sliding clamp in mediating switches between high fidelity and error-prone lesion bypass DNA polymerases, as well as the contribution of these switches to DNA fidelity and DNA damage tolerance.

Selected Publications

Sanders, L. H., Wozniak, D. J. and Sutton, M. D. Accurate and error-prone roles for DinB in modulating the mutation frequency of P. aeruginosa deficient in mismatch repair functions. Submitted
.
Maul, R. W., Scouten-Ponticelli, S., Duzen, J. M., and Sutton, M. D. (2007). Differential binding of E. coli DNA polymerases to the b-sliding clamp. Molecular Microbiology. 65(3):811-827.

Maul, R. W., Sanders, L. H., Lim, J., Benetiz, R. and Sutton, M. D. (2007). Role of Escherichia coli DNA polymerase I in conferring viability upon the dnaN159 mutant strain. Journal of Bacteriology. 189:4688-4695; published on-line Apr. 20, 2007.

Sanders, L. H., Rockel, A., Lu, H., Wozniak, D. J., and Sutton, M. D. (2006). Role of the P. aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. Journal of Bacteriology. 188:8573-8585; published on-line Oct. 13, 2006.

Sutton, M. D. and Duzen, J.M. (2006). Specific amino acid residues in the b sliding clamp establish a DNA polymerase usage hierarchy in Escherichia coli. DNA Repair. 5:312-323; published on-line Dec. 7, 2005.

Maul, R. W. and Sutton, M. D. (2005). Roles of the Escherichia coli RecA protein and the global SOS response in effecting DNA polymerase selection in vivo. Journal of Bacteriology. 187:7607-7618.

Sutton, M.D., Duzen, J.M. and Maul R.W. (2005). mutant forms of the Escherichia coli b sliding clamp that distinguish between its roles in replication and DNA polymerase V-dependent translesion DNA synthesis. Molecular Microbiology. 55:1751-1766.

Sutton, M.D. (2004). The Escherichia coli dnaN159 mutant displays altered DNA polymerase usage and chronic SOS induction. Journal of Bacteriology.  186:6738-6748.

Duzen, J.M., Walker, G.C. and Sutton, M.D. (2004). Identification of specific amino acid residues in the E. coli b processivity clamp involved in interactions with DNA polymerase III, UmuD and UmuD’. DNA Repair. 3:301-312.

Maul RW. Ponticelli SK. Duzen JM. Sutton MD. Differential binding of Escherichia coli DNA polymerases to the beta-sliding clamp. Molecular Microbiology. 65(3):811-27, 2007 Aug.

Sanders LH. Rockel A. Lu H. Woszniak DJ. Sutton MD. Role of Pseudomonas as aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. Journal of Bacteriology. 188(24):8573-85, 2006 Dec.

 

BOOK CHAPTERS

Sutton, M.D. (2005). Damage Signals Triggering the E. coli SOS Response. In: DNA Damage Recognition, Chapter 35, pages 781-802. Eds. W. Siede, Y. W. Kow, and P. W. Doetsch, Marcel-Decker, Inc., New York, NY.

Walker, G. C., Smith, B. T., and Sutton, M. D.  (2000). The SOS Response to DNA Damage.  In: Bacterial Stress Responses, Chapter 9, pages 131-144.  Eds. G. Stroz and R. Hengge-Aronis, ASM Press, Washington DC.

 

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