DNA segregation under Par protein control

Abstract

The spatial organization of DNA is mediated by the Par protein system in some bacteria. ParB binds specifically to the parS sequence on DNA and orchestrates its motion by interacting with ParA bound to the nucleoid. In the case of plasmids, a single ParB bound plasmid is observed to execute oscillations between cell poles while multiple plasmids eventually settle at equal distances from each other along the cell’s length. While the potential mechanism underlying the ParA-ParB interaction has been discussed, it remains unclear whether ParB-complex oscillations are stable limit cycles or merely decaying transients to a fixed point. How are dynamics affected by substrate length and the number of complexes? We present a deterministic model for ParA-ParB driven DNA segregation where the transition between stable arrangements and oscillatory behaviour depends only on five parameters: ParB-complex number, substrate length, ParA concentration, ParA hydrolysis rate and the ratio of the lengthscale over which the ParB complex stimulates ParA hydrolysis to the lengthscale over which ParA interacts with the ParB complex. When the system is buffered and the ParA rebinding rate is constant we find that ParB-complex dynamics is independent of substrate length and complex number above a minimum system size. Conversely, when ParA resources are limited, we find that changing substrate length and increasing complex number leads to counteracting mechanisms that can both generate or subdue oscillatory dynamics. We argue that cells may be poised near a critical level of ParA so that they can transition from oscillatory to fixed point dynamics as the cell cycle progresses so that they can both measure their size and faithfully partition their genetic material. Lastly, we show that by modifying the availability of ParA or depletion zone size, we can capture some of the observed differences in ParB-complex positioning between replicating chromosomes in B. subtilis cells and low-copy plasmids in E. coli cells.

Optimizing Efficiency and Motility of a Polyvalent Molecular Motor

“…The substrate can exist in one of three states: (i) surface-bound, (ii) bound to the hub or (iii) free in the buffer (Figure 1A). (This extends our previous model that did not explicitly consider the dynamics of the substrate-hub complex) [4,23]. The concentration of surface-bound substrate on the track at position X is A s (X).…”

High-throughput imaging and quantitative analysis uncovers the nature of plasmid positioning by ParABS

“…Furthermore, while oscillatory dynamics have been observed, it was not clear whether this is representative of how these systems operate. On the modelling side, there have been several studies, both deterministic ( Adachi et al, 2006 ; Ietswaart et al, 2014 ; Jindal and Emberly, 2019 ; Sugawara and Kaneko, 2011 ; Walter et al, 2017 ) and stochastic ( Hu et al, 2021 ; Hu et al, 2017 ; Ietswaart et al, 2014 ; Surovtsev et al, 2016a ), each producing some set of dynamical behaviours. However, the lack of quantitative dynamical measurements has meant that none of these models has been quantitatively compared or tested against experimental observations.…”

“…Indeed, both F plasmid and pB171 have been described as exhibiting oscillatory dynamics as they follow corresponding changes in the ParA gradient, which may also lead to regular positioning as a time-averaged effect ( Hatano et al, 2007 ; Ringgaard et al, 2009 ; Surovtsev et al, 2016a ). While there have been several modelling studies of plasmid positioning ( Adachi et al, 2006 ; Ietswaart et al, 2014 ; Jindal and Emberly, 2019 ; Ringgaard et al, 2009 ; Sugawara and Kaneko, 2011 ; Walter et al, 2017 ) and, in particular, two recent stochastic models that incorporate the molecular mechanism of force generation ( Hu et al, 2017 ; Surovtsev et al, 2016a ), the lack of quantitative measurements of plasmid dynamics has hindered their evaluation. This is especially important as it may be challenging to distinguish noisy true positioning from approximate positioning or noisy low-amplitude oscillations.…”

DivIVA Controls Progeny Morphology and Diverse ParA Proteins Regulate Cell Division or Gliding Motility in Bdellovibrio bacteriovorus

“…In many bacteria, chromosomal segregation during cell division is controlled by the three element ParABS system via a ratchet diffusion model, as recently reviewed (Jindal and Emberly, 2019). ParB binds to centromere-like parS DNA sequences forming the ParBS nucleoprotein complex.…”