Multicopy plasmid instability: the dimer catastrophe hypothesis.

Abstract:

:Multimer formation reduces plasmid copy number and is an established cause of segregational instability. Nevertheless, it is difficult to rationalize observations that low levels of dimers can cause severe instability, if we assume they are distributed evenly in cell populations. We report here that dimer distribution is in fact heterogeneous in recombination-proficient strains. Most cells in the population contain only monomers; dimers are confined to a small subpopulation from which plasmid-free daughters arise at high frequency. In a rec+ culture where 4% of pBR322 molecules are dimers, more than half are in dimer-only cells. We show that this situation is inevitable because dimers replicate at twice the rate of monomers. Runaway multimerization is avoided because dimer-containing cells grow more slowly than their monomer-containing counterparts. A computer simulation is used to show how dimers proliferate after formation by homologous recombination. The equilibrium concentration of dimers is proportional to the inter-plasmid recombination rate and is essentially independent of the rate at which homologous recombination converts dimers to monomers.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Summers DK,Beton CW,Withers HL

doi

10.1111/j.1365-2958.1993.tb01648.x

subject

Has Abstract

pub_date

1993-06-01 00:00:00

pages

1031-8

issue

6

eissn

0950-382X

issn

1365-2958

journal_volume

8

pub_type

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