title: High-affinity quasi-specific sites in the genome: how the DNA-binding proteins cope with them.
abstract: Many prokaryotic transcription factors home in on one or a few target sites in the presence of a huge number of nonspecific sites. Our analysis of λ-repressor in the Escherichia coli genome based on single basepair substitution experiments shows the presence of hundreds of sites having binding energy within 3 Kcal/mole of the O(R)1 binding energy, and thousands of sites with binding energy above the nonspecific binding energy. The effect of such sites on DNA-based processes has not been fully explored. The presence of such sites dramatically lowers the occupation probability of the specific site far more than if the genome were composed of nonspecific sites only. Our Brownian dynamics studies show that the presence of quasi-specific sites results in very significant kinetic effects as well. In contrast to λ-repressor, the E. coli genome has orders of magnitude lower quasi-specific sites for GalR, an integral transcription factor, thus causing little competition for the specific site. We propose that GalR and perhaps repressors of the same family have evolved binding modes that lead to much smaller numbers of quasi-specific sites to remove the untoward effects of genomic DNA.
authors: Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, CSIR-Indian Institute of Chemical Biology, Kolkata, India. jaydeb@bose.res.in
authors: J
authors: J
authors: Chakrabarti
authors: Navin
authors: N
authors: Chandra
authors: Paromita
authors: P
authors: Raha
authors: Siddhartha
authors: S
authors: Roy
mesh_terms: D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D016680:Genome, Bacterial / Q000235:genetics*; D007700:Kinetics; D008954:Models, Biological; D012097:Repressor Proteins / Q000378:metabolism; D013816:Thermodynamics; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C050993:Galactose repressor proteins; D012097:Repressor Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins