Effects of macromolecular crowding and DNA looping on gene regulation kinetics.
2009 (English)In: Nature Physics, ISSN 1745-2473, E-ISSN 1745-2481, Vol. 5, no 4, 294-297 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2009. Vol. 5, no 4, 294-297 p.
IdentifiersURN: urn:nbn:se:uu:diva-129116DOI: 10.1038/NPHYS1222ISI: 000265264500021OAI: oai:DiVA.org:uu-129116DiVA: diva2:337670