Review The 2 micron plasmid of Saccharomyces cerevisiae: A miniaturized selfish genome with optimized functional competence Keng-Ming Chan, Yen-Ting Liu, Chien-Hui Ma, Makkuni Jayaram, Soumitra Sau ⇑ Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78712, United States article info Article history: Available online 27 March 2013 Communicated by Dr. F. de la Cruz Keywords: Selfish DNA Plasmid partitioning Chromosome-hitchhiking Site-specific recombination Plasmid amplification Difference topology abstract The 2 micron plasmid of Saccharomyces cerevisiae is a relatively small multi-copy selfish DNA element that resides in the yeast nucleus at a copy number of 40–60 per haploid cell. The plasmid is able to persist in host populations with almost chromosome-like stability with the help of a partitioning system and a copy number control system. The first part of this article describes the properties of the partitioning system comprising two plasmid coded proteins, Rep1 and Rep2, and a partitioning locus STB. Current evidence supports a model in which the Rep-STB system couples plasmid segregation to chromosome segrega- tion by promoting the physical association of plasmid molecules with chromosomes. In the second part, the focus is on the Flp site-specific recombination system housed by the plas- mid, which plays a critical role in maintaining steady state plasmid copy number. The Flp system corrects any decrease in plasmid population by promoting plasmid amplification via a recombination induced rolling circle replication mechanism. Appropriate plasmid amplification, without runaway increase in copy number, is ensured by positive and neg- ative regulation of FLP gene expression by plasmid coded proteins and by the control of Flp level/activity through post-translational modification of Flp by the cellular sumoylation system. The Flp system has been successfully utilized to understand mechanisms of site- specific recombination and to bring about directed genetic alterations for addressing fun- damental problems in biology and for accomplishing bio-engineering objectives. A partic- ularly interesting, and perhaps less well known and underappreciated, application of Flp in revealing unique DNA topologies required to confer functional competence to DNA–protein machines is discussed. Published by Elsevier Inc. Contents 1. Introduction .............................................................................................. 3 2. The 2 micron circle: genome organization and function ........................................................... 3 3. Organization of 2 micron plasmid molecules in the nucleus: implications for segregation ............................... 4 4. The 2 micron plasmid partitioning system: a molecular design for coupling plasmid segregation to chromosome segregation?. 4 5. Organization of the 2 micron plasmid partitioning system......................................................... 5 6. The STB locus: associations with Rep proteins and host factors ..................................................... 6 7. The budding yeast centromere (CEN) and STB: a shared evolutionary ancestry? ....................................... 7 8. Nearly conflict-free coexistence of the yeast plasmid with its host genome? .......................................... 7 0147-619X/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.plasmid.2013.03.001 ⇑ Corresponding author. Fax: +1 512 471 0966. E-mail address: jayaram@austin.utexas.edu (S. Sau). Plasmid 70 (2013) 2–17 Contents lists available at SciVerse ScienceDirect Plasmid journal homepage: www.elsevier.com/locate/yplas