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A nonequilibrium strategy for fast target search on the genome

F. Cagnetta, View ORCID ProfileD. Michieletto, View ORCID ProfileD. Marenduzzo
doi: https://doi.org/10.1101/2020.04.28.065524
F. Cagnetta
1SUPA, School of Physics and Astronomy, University of Edinburgh, Edinburgh EH9 3FD, United Kingdom
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D. Michieletto
1SUPA, School of Physics and Astronomy, University of Edinburgh, Edinburgh EH9 3FD, United Kingdom
2MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
3Department of Mathematical Sciences, University of Bath, North Rd, Bath BA2 7AY, United Kingdom
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D. Marenduzzo
1SUPA, School of Physics and Astronomy, University of Edinburgh, Edinburgh EH9 3FD, United Kingdom
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  • For correspondence: davide.marenduzzo@ed.ac.uk
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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 colours (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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 29, 2020.
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A nonequilibrium strategy for fast target search on the genome
F. Cagnetta, D. Michieletto, D. Marenduzzo
bioRxiv 2020.04.28.065524; doi: https://doi.org/10.1101/2020.04.28.065524
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A nonequilibrium strategy for fast target search on the genome
F. Cagnetta, D. Michieletto, D. Marenduzzo
bioRxiv 2020.04.28.065524; doi: https://doi.org/10.1101/2020.04.28.065524

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