Martin L. Pato

Associate Professor Ph.D., University of California at Berkeley

Current Research

The research interests of my laboratory have been in the area of the physiology and molecular biology of bacteria and bacteriophages. For some time, the primary focus has been on the mechanism of genetic transposition and the biology of bacteriophage Mu. Mu has proven to be the premier biological system for studying transposition, due largely to our ability to study transposition events in the entirety of a population rather than as a rare event as with most other transposable elements. Most recently, the work has led to studies on the role of strong DNA gyrase binding sites and DNA topology in Mu transposition and the potential role of strong gyrase sites in chromosomal organization.

While in a host cell, Mu DNA is always integrated into host chromosomal DNA. To replicate or transpose Mu DNA, the ends of the prophage DNA must be brought together while constrained within the host DNA. The focus of most of my recent work is a model to explain how the Mu prophage termini are synapsed - an essential early step in transposition. I proposed that a site in the center of the genome organizes the topology of prophage DNA to form a supercoiled loop with the central site at the apex of the loop and the termini brought together at the base of the loop, where they can then be synapsed by Mu transposase bound at both termini. I predicted the presence of, and found, an unusually strong DNA gyrase binding site in the center of the genome, and showed that deletion of the site inhibited Mu replication. Rigorous tests of the model that the gyrase binding site is responsible for organizing the topology of prophage DNA to allow synapsis of the prophage ends have led us to believe that the model is correct.

The present and future direction of the research will take several forms, including: detailed analysis of: a) the role of the Mu strong gyrase binding site in transposition, b) the potential use of strong gyrase binding sites in organizing supercoiled DNA structure in other viruses and in bacteria, and c) the potential role of strong gyrase binding sites as preferred targets of the classes of antibiotics, such as the quinolones, which specifically target gyrase bound to DNA.

Recent Publications

Click Here For An Updated List Of Dr. Pato's Publications

Oram M, Travers AA, Howells AJ, Maxwell A, Pato ML. Dissection of the bacteriophage Mu strong gyrase site (SGS): significance of the SGS right arm in Mu biology and DNA gyrase mechanism. J Bacteriol. 2006 Jan;188(2):619-32.

Pato, M.L. (2004) Replication of Mu prophages lacking the central strong gyrase site. Res Microbiol. 155(7):553-8.

Oram, M and Pato, M.L.(2004) Mu-like prophage strong gyrase site sequences: analysis of properties required for promoting efficient mu DNA replication. J Bacteriol. 186(14):4575-84.

Oram, M., Howells, A., Maxwell, A., and Pato, M.L. (2003) A biochemical analysis of the interaction of DNA gyrase with the bacteriophage Mu, pSC101 and pBR322 strong gyrase sites: the role of DNA sequence in modulating gyrase supercoiling and biological activity. Molec. Microbiol. 50(1):333-347.