| Resumo: |
Plasmids are small circular DNA molecules in bacteria which replicate sharing the replication machinery with the bacterial chromosome. Since plasmids are much smaller than the chromosome, unless their replication is tightly regulated, their copy numbers can escalate quickly. A number of mechanisms of plasmid replication regulation are known in P1 plasmid of E. coli. Mechanisms such as autorepression of the replication initiator protein (RepA) and its dimerization are unable to explain copy number regulation by themselves. The number of RepA binding sites (iterons) is inversely related to copy numbers. Handcuffing of plasmids by RepA dimer is believed to be the main mechanism of arresting replication. We show here with a probabilistic model that for the handcuffing mechanism to work, a certain iteron number is critical without which handcuffing is unlikely to work. Further, RepA autorepression, dimerization, iteron number and handcuffing mechanism need to work in concert and no single mechanism in isolation is able to regulate plasmid replication effectively. The model also makes quantitative predictions that can be tested experimentally.
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