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Effects of macromolecular crowding and DNA looping on gene regulation kinetics.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Molekylär evolution.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Bioinformatik.
2009 (engelsk)Inngår i: Nature Physics, ISSN 1745-2473, E-ISSN 1745-2481, Vol. 5, nr 4, s. 294-297Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

DNA-binding proteins control how genomes function. The theory of facilitated diffusion(1) explains how DNA-binding proteins can find targets apparently faster than the diffusion limit by using reduced dimensionality(2,3)-combining three-dimensional (3D) diffusion through cytoplasm with 1D sliding along DNA (refs 3-15). However, it does not include a description of macromolecular crowding on DNA as observed in living cells. Here, we show that such a physical constraint to sliding greatly reduces the search speed, in agreement with single-molecule measurements. Interestingly, the generalized theory also reveals significant insights into the design principles of biology. First, it places a hard constraint on the total number of DNA-binding proteins per cell. Remarkably, the number measured for Escherichia coli fits within the optimal range. Secondly, it defines a new role for DNA looping, a ubiquitous topological motif in genomes. DNA looping can speed up the search process by bypassing proteins that block the sliding track close to the target.

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2009. Vol. 5, nr 4, s. 294-297
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URN: urn:nbn:se:uu:diva-129116DOI: 10.1038/NPHYS1222ISI: 000265264500021OAI: oai:DiVA.org:uu-129116DiVA, id: diva2:337670
Tilgjengelig fra: 2010-08-09 Laget: 2010-08-05 Sist oppdatert: 2017-12-12bibliografisk kontrollert

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