Nonequilibrium Strategy for Fast Target Search on the Genome

Davide Michieletto, Francesco Cagnetta, Davide Marenduzzo

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Abstract

Vital biological processes such as genome repair require fast and efficient binding of selected proteins to specific target sites on DNA. Here we propose an active target search mechanism based on “chromophoresis,” the dynamics of DNA-binding proteins up or down gradients in the density of epigenetic marks, or colors (biochemical tags on the genome). We focus on a set of proteins that deposit marks from which they are repelled—a case which is only encountered away from thermodynamic equilibrium. For suitable ranges of kinetic parameter values, chromophoretic proteins can perform undirectional motion and are optimally redistributed along the genome. Importantly, they can also locally unravel a region of the genome which is collapsed due to self-interactions and “dive” deep into its core, for a striking enhancement of the efficiency of target search on such an inaccessible substrate. We discuss the potential relevance of chromophoresis for DNA repair.
Original languageEnglish
Article number198101
JournalPhysical Review Letters
Volume124
Issue number19
DOIs
Publication statusPublished - 15 May 2020

ASJC Scopus subject areas

  • Physics and Astronomy(all)

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