Physical modeling of a sliding clamp mechanism for the spreading of ParB at short genomic distance from bacterial centromere sites

• DOI: 10.1101/2020.07.22.213413
• Publication Date: 2020-07-24T21:05:45Z
• Authors: Jean-Charles Walter; Jérôme Rech; Nils-Ole Walliser; Jérôme Dorignac; Frédéric Geniet; John Palmeri; Andrea Parmeggiani; Jean-Yves Bouet
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; [SDV]Life Sciences [q-bio]; [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]; Systems Biology; Science; Gene Process; Q; Microbial Genetics; Article

AbstractBacterial ParB partitioning proteins involved in chromosomes and low-copy-number plasmid segregation have recently been shown to belong to a new class of CTP-dependent molecular switches. Strikingly, CTP binding and hydrolysis was shown to induce a conformational change enabling ParB dimers to switch between an open and a closed conformation. This latter conformation clamps ParB dimers on DNA molecules, allowing their diffusion in one dimension along the DNA. It has been proposed that this novel sliding property may explain the spreading capability of ParB over more than 10-Kb fromparScentromere sites where ParB is specifically loaded. Here, we modeled such a mechanism as a typical reaction-diffusion system and compared this ‘Clamping & sliding’ model to the ParB DNA binding pattern from high-resolution ChIP-sequencing data. We found that this mechanism cannot account for all thein vivocharacteristics, especially the long range of ParB binding to DNA. In particular, it predicts a strong effect from the presence of a roadblock on the ParB binding pattern that is not observed in ChIP-seq. Moreover, the rapid assembly kinetics observedin vivoafter the duplication ofparSsites is not easily explained by this mechanism. We propose that ‘Clamping & sliding’ might explain the ParB spreading pattern at short distances fromparSbut that another mechanism must apply for ParB recruitment at larger genomic distances.