The yeast plasmid 2 micron circle provides a simple experimental paradigm for the evolution of a selfish genome (or a benign molecular parasite). The genetic content and organization of this DNA molecule is devoted to maintaining itself stably in a population without unduly straining the metabolic machinery plasmid molecules at cell division. An amplification system, also encoded by the plasmid, adjusts plasmid copy number back to normal if and when it drops due to an occasional failure in partitioning. The amplification system must be exquisitely regulated for two reasons. First, it must be repressed under steady state growth, so that uncontrolled increase in copy number does not pose a threat to the host, and consequently to plasmid survival. Second, in the event of a fall in copy number, it must be commissioned immediately, so that copy number can be restored to the normal value within a short time. This project attempts to understand two aspects of the amplification mechanism. First, we wish to consider possible models for amplification, and test their predictions by using suitably designed plasmid substrates. Second we wish to analyze what biochemical steps mediated by the Flp recombinase, the central component of the amplification system, are important in the production of multiple plasmid copies from a single replication initiation event.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM062167-03
Application #
6619707
Study Section
Genetics Study Section (GEN)
Program Officer
Wolfe, Paul B
Project Start
2001-08-01
Project End
2005-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
3
Fiscal Year
2003
Total Cost
$232,915
Indirect Cost
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Liu, Yen-Ting; Sau, Saumitra; Ma, Chien-Hui et al. (2014) The partitioning and copy number control systems of the selfish yeast plasmid: an optimized molecular design for stable persistence in host cells. Microbiol Spectr 2:
Harshey, Rasika M; Jayaram, Makkuni (2006) The mu transpososome through a topological lens. Crit Rev Biochem Mol Biol 41:387-405