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• W3048875949 abstract "Bacterial genomes have been shown to be partitioned into several-kilobase-long chromosomal domains that are topologically independent from each other, meaning that change of DNA superhelicity in one domain does not propagate to neighbors. Both in vivo and in vitro experiments have been performed to question the nature of the topological barriers at play, leading to several predictions on possible molecular actors. Here, we address the question of topological barriers using polymer models of supercoiled DNA chains that are constrained such as to mimic the action of predicted molecular actors. More specifically, we determine under which conditions DNA-bridging proteins may act as topological barriers. To this end, we developed a coarse-grained bead-and-spring model and investigated its properties through Brownian dynamics simulations. As a result, we find that DNA-bridging proteins must exert rather strong constraints on their binding sites; they must block the diffusion of the excess of twist through the two binding sites on the DNA molecule and, simultaneously, prevent the rotation of one DNA segment relative to the other one. Importantly, not all DNA-bridging proteins satisfy this second condition. For example, single bridges formed by proteins that bind DNA nonspecifically, like H-NS dimers, are expected to fail with this respect. Our findings might also explain, in the case of specific DNA-bridging proteins like LacI, why multiple bridges are required to create stable independent topological domains. Strikingly, when the relative rotation of the DNA segments is not prevented, relaxation results in complex intrication of the two domains. Moreover, although the value of the torsional stress in each domain may vary, their differential is preserved. Our work also predicts that nucleoid-associated proteins known to wrap DNA must form higher protein-DNA complexes to efficiently work as topological barriers." @default.
• W3048875949 created "2020-08-18" @default.
• W3048875949 creator A5028173735 @default.
• W3048875949 creator A5047786562 @default.
• W3048875949 date "2020-09-01" @default.
• W3048875949 modified "2023-09-30" @default.
• W3048875949 title "Requirements for DNA-Bridging Proteins to Act as Topological Barriers of the Bacterial Genome" @default.
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• W3048875949 doi "https://doi.org/10.1016/j.bpj.2020.08.004" @default.
• W3048875949 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7420610" @default.
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