Functional analysis of a palindromic sequence required for normal replication of several staphylococcal plasmids

Most small multicopy antibiotic-resistance plasmids of Staphylococcus aureus contain a major axis of hyphenated dyad symmetry (palA) that is required for normal replication and stability, although located outside of the minimal replicon. Rearrangements affecting palA cause plasmid instability, a marked reduction in copy number, and the accumulation of large quantities of strand-specific circular single-stranded plasmid DNA. In view of the recent observation that pT181 initiates replication by a nick and 3'-extension mechanism (S. Khan, personal communication), it is suggested that these plasmids replicate by an asymmetric rolling-circle mechanism in which the displaced plus strand remains single stranded until palA is exposed, forming a hairpin that serves as the lagging strand origin.