Closing the Loop on Protein-DNA Interactions: Interplay Between Shape and Flexibility in Nucleoprotein Assemblies Having Implications for Biological Regulation
The formation of DNA loops by proteins bound at distant sites along a single molecule is an essential mechanistic aspect of many biological processes including gene regulation, DNA replication, and recombination. The biological importance of DNA loop formation is underscored by an abundance of architectural proteins in cells such as HU, IHF, and HMGs, which facilitate looping by bending the intervening DNA between cognate protein-binding sites. We have developed a rigorous theory for DNA loop formation that connects the global mechanical and geometric properties of both DNA and protein, including previously neglected phenomena such as the conformational flexibility of protein domains. The theory is applied to the problem of loop-mediated gene repression in vivo by lac repressor.
Key wordsDNA looping wormlike chain J factor gene regulation lac repressor AMS(MOS) subject classifications Primary 92C05 92C40 82D60
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- J. Yan, R. Kawamura, and J.F. Marko, Statistics of loop formation along doubl helix DNAs. Phys. Rev. E. Stat. Nonlin. Soft. Matter. Phys. 71: 061905, 2005.Google Scholar
- D. Normanno, F. Vanzi, and F.S. Pavone, Single-molecule manipulation reveals supercoiling-dependent modulation of lac repressor-mediated DNA looping. Nucleic Acids Res., 2008.Google Scholar
- V.A. Bloomfield, D.M. Crothers, and I.J. Tinoco, 2000. Nucleic Acids: Struc-tures, Properties and Functions. University Science Books, Herndon, VA. 800.Google Scholar
- K.V. Klenin, A.V. Vologodskii, V.V. Anshelevich, V. Klishko, A.M. Dykhne, and M.D. Frank-Kamenetskii, Variance of writhe for wormlike DNA rings with excluded volume. J. Biomol. Struct. Dyn. 6: 707–714, 1989.Google Scholar
- H. Benjamin and N. Cozzarelli, DNA-directed synapsis in recombination: Slith-ering and random collision of sites. The Robert A. Welch Foundation Confer-ences on Chemical Research 29: 107–126.Google Scholar
- S.M. Law, G.R. Bellomy, P.J. Schlax, and M.T. Record, In-vivo thermo-dynamic analysis of repression with and without looping in lac constructs -estimates of free and local lac repressor concentrations and of physical proper ties of a region of supercoiled plasmid DNA in vivo. J. Mol. Biol. 230: 161–173, 1993.CrossRefGoogle Scholar
- P.H. von Hippel, On the molecular bases of the specificity of interaction of tran-scriptional proteins with genome DNA. In Biological Regulation and Development, R. F. Goldberger, editor. Plenum, New York, pp. 279–347, 1979.Google Scholar
- S. Sasse-DwighT and J.D. Gralla, Probing co-operative DNA-binding in vivo.The lac O1:O3 interaction. J. Mol. Biol. 202: 107–119, 1988.Google Scholar