DNA looping

FIGURE 12.31 A model for chromosome structure, human chromosome 4. The 2-um DNA helix is wound twice around histone octamers to form 10-um uucleosomes, each of which contains 160 bp (80 per turn). These uucleosomes are then wound in solenoid fashion with six uucleosomes per turn to form a 30-nm filament. In this model, the 30-nm filament forms long DNA loops, each containing about 60,000 bp, which are attached at their base to the nuclear matrix. Eighteen of these loops are then wound radially around the circumference of a single turn to form a miniband unit of a chromosome. Approximately 10 of these minibands occur in each chromatid of human chromosome 4 at mitosis. 

The low torsion constant at a = —0.025 is very similar to that observed in a supercoiled pBR322 that was partially relaxed by saturation binding of Escherichia coli single-strand binding (ssb) protein, and which persisted for over a month.(56) It is also similar to that recently inferred from an in vivo assay based on variation in repression efficiency with size of a putative DNA loop.(234) Indeed, it appears that anomalously low torsion constants may be universally encountered in the course of either partial or complete relaxation of supercoiled DNAs, regardless of whether the superhelix density is reduced by action of topoisomerase I, binding of ssb protein, binding of intercalated... 

Razin SV, Petrov P, Hancock R (1991) Precise localization of the alpha-globin gene cluster within one of the 20- to 300-kilobase DNA fragments released by cleavage of chicken chromosomal DNA at topoisomerase 11 sites in vivo evidence that the fragments are DNA loops or domains. Proc Natl Acad Sci USA 88(19) 8515-8519... 

Smith HC, Berezney R (1980) DNA polymerase alpha is tightly bound to the nuclear matrix of actively replicating liver. Biochem Biophys Res Commun 97(4) 1541-1547 Smith HC, Puvion E, Buchholtz LA, Berezney R (1984) Spatial distribution of DNA loop attachment and replicational sites in the nuclear matrix. J Cell Biol 99(5) 1794-1802 Sperry AO, Blasquez VC, Garrard WT (1989) Dysfunction of chromosomal loop attachment sites Illegitimate recombination linked to matrix association regions and topoisomerase 11. Proc Natl Acad Sci USA 86(14) 5497-5501... 

C. Vaillant, B. Audit, and A. Arneodo, Thermodynamics of DNA loops with long-range correlated structural disorder. Phys. Rev. Lett. 95, 068101 (2005). 

Angelov, D., Vitolo, J.M., Mutskov, V., Dimitrov, S., and Hayes, J.J. (2001) Preferential interaction of the core histone tail domains with linker DNA. Proc. Natl. Acad. Sci. USA 98, 6599-6604. Tobias, I., Coleman, B.D., and Olson, W. (1994) The dependence of DNA tertiary structure on end conditions theory and implications for topological transitions. J. Chem. Phys. 101, 10990-10996. Coleman, B.D., Tobias, I., and Swigon, D. (1995) Theory of the influence of end conditions on selfcontact in DNA loops. J. Chem. Phys. 103, 9101-9109. 

Stros, M., Stokrova, J., and Thomas, J.O. (1994) DNA looping by theHMG-box domains of HMGl and modulation of DNA binding by the acidic C-terminal domain. Nucleic Acids Res. 22, 1044-1051. 

Pauli, T.T. and Johnson, R.C. (1995) DNA looping by Saccharomyces cerevisiae high mobility group proteins NHP6A/B. Consequences for nucleoprotein complex assembly and chromatin condensation. J. Biol. Chem. 270, 8744-8754. 

Ringrose, L., Chabanis, S., Angrand, P.O., Woodroofe, C., and Stewart, A.F. (1999) Quantitative comparison of DNA looping in vitro and in vivo chromatin increases effective DNA flejdbihty at short distances. EMBO J. 18, 6630-6641. 

Another possible location for histone HI or H5 is above the histone surface as shown in Fig. 27-4 and inside the DNA loop.65 A third suggested location for the globular linker core is between the two turns of the DNA strand.66 While one function of the linker histones may be to stabilize mononucleosomes, they may also play a role in compaction of the DNA into the 30-nm fibers universally seen in nuclei of cells.62 64-640... 

Figure 27-20 (A) Hypothetical replisome for concurrent replication of leading and lagging strands by a dimeric polymerase associated with helicase dnaB and a primosome. Open arrows indicate directions of movement of DNA, which is forming a loop as the polymerase fills a gap to complete an Okazaki fragment. The primase will then form a new primer and a new loop. From Komberg and Baker.265 (B) Electron micrograph of the primosome bound to covalently closed ( )X174 duplex replicative form. These enzymatically synthesized duplexes invariably contain a single primosome with one or two associated small DNA loops. From A. Komberg in Hubscher and Spadari,266 pp. 9,10.

Figure 28-3 (A) Ribbon view of the dimeric lac repressor bound to a natural operator and to the anti-inducer o-nitro-phenylfucoside (ONPF). The headpiece (residues 2-46) and the hinge helix (residues 50-58) form the DNA-binding domains. The core (residues 62-330), which is divided into N- and C-terminal subdomains, forms the binding site for ONPF. The C-terminal residues 334-360, which form a tetramerization domain, are absent from this MolScript drawing. Notice that the hinge helices bind to and widen the minor groove at the center of the operator. From Lewis et al.5a (B) Model of a 93-bp DNA loop corresponding to residues -82 to +11 of the lac operon (Fig. 28-2) bound to the tetrameric lac repressor. The active sites of the repressor are bound to the major operator O, and to the secondary operator 03. From Lewis et al.5...

Kinetics involving rapid pre-equilibrium steps finds numerous applications both within and beyond the study of enzyme kinetics. Other important examples are the theory of proton-deuterium exchange kinetics of a protein [169] and gene activation involving DNA looping [186], Because of its central importance in biological kinetics, let us provide a more complete mathematical treatment of the problem in a short digression. 

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