Spatial effects on the speed and reliability of protein-DNA search
arXiv:0708.1136 · doi:10.1093/nar/gkn173
Abstract
Strong experimental and theoretical evidence shows that transcription factors and other specific DNA-binding proteins find their sites using a two-mode search: alternating between 3D diffusion through the cell and 1D sliding along the DNA. We consider the role spatial effects in the mechanism on two different scales. First, we reconcile recent experimental findings by showing that the 3D diffusion of the transcription factor is often local, i.e. the transcription factor lands quite near its dissociation site. Second, we discriminate between two types of searches: global searches and local searches. We show that these searches differ significantly in average search time and the variability of search time. Using experimentally measured parameter values, we also show that 1D and 3D search is not optimally balanced, leading to much larger estimates of search time. Together, these results lead to a number of biological implications including suggestions of how prokaryotes and eukaryotes achieve rapid gene regulation and the relationship between the search mechanism and noise in gene expression.
16 pages, 4 figures
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- Mesoscopic Model for Free Energy Landscape Analysis of DNA sequences
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- Theory on the mechanism of site-specific DNA-protein interactions in the presence of traps
- Accelerated search kinetics mediated by redox reactions of DNA repair enzymes
- Design principles of transcription factors with intrinsically disordered regions
- Theory on the mechanisms of combinatorial binding of transcription factors with DNA