Ph.D., Polish Academy of Sciences Institute of Biochemistry and Biophysics, 1979
Postdoctoral Research: University of California-San Diego
Address: 6305 Microbial Sciences Building
Regulation of DNA replication and transcription
Duplication of stably inherited replicons
such as chromosomes or plasmids is regulated early in the synthesis of
DNA. Thus, the initiation of replication at specific sites on the DNA
(origins) is one of the most fundamental biological processes. Work in
our laboratory is directed toward deciphering the molecular strategies
underlying the regulated initiation of DNA replication.
Control circuits regulating initiation must ensure that the average replication rate is less than once per generation in cells with too many replicons and more than once per generation in cells with too few. Although the basic requirements for copy control are quite simple, the actual mechanisms which are employed to control replication are diverse and complex (1, 2). For many replicons, specific initiator proteins precisely localize the origin through binding to reiterated DNA sequences. This binding promotes a series of protein-protein interactions culminating in the development of the replication fork. Our laboratory is investigating the multiple levels of control necessary for positive and negative regulation of replication using an antibiotic resistance plasmid, R6K. We study both the protein-DNA (3) and the protein-protein (4) communications which are central to the regulatory control of DNA replication.
Our laboratory is also developing new antibacterial technologies that are attractive alternatives to conventional pharmaceutical antibiotics.
Kruger, R. and M. Filutowicz. 2000. Dimers
of p protein bind the A+T-rich region of the R6K g ori near the leading
strand synthesis start sites: Regulatory implications. J. Bacteriol.
Chen, D., J. Feng, R. Kruger, M. Urh, R.B. Inman and M. Filutowicz 1998. Discrete start sites for in vitro DNA synthesis at the R6K g origin dependent on wt and copy-up variants of p35.0 are the same. J. Mol. Biol. 282:775-787.
Filutowicz, M. and S.A. Rakowski 1998. Regulatory implications of protein assemblies at the g ori of plasmid R6K- a review. Gene 223:195-204.
Urh, M., J. Wu, K. Forest, R.B. Inman and M. Filutowicz. 1998. Assemblies of replication initiator protein on symmetric and asymmetric DNA sequences depend on multiple protein surfaces. J. Mol. Biol. 283:619-631.