DNA Spools under Tension

Abstract

DNA-spools, structures in which DNA is wrapped and helically coiled onto itself or onto a protein core are ubiquitous in nature. We develop a general theory describing the non-equilibrium behavior of DNA-spools under linear tension. Two puzzling and seemingly unrelated recent experimental findings, the sudden quantized unwrapping of nucleosomes and that of DNA toroidal condensates under tension are theoretically explained and shown to be of the same origin. The study provides new insights into nucleosome and chromatin fiber stability and dynamics. as a means to efficiently pack and transport DNA into cells. In most of these ligand-DNA complexes the geometry and chemistry of the ligand surface enforces the DNA to follow a superhelical wrapping path with one or more tight turns. Remarkably, upon addition of multivalent condensing agents (like in sperm cells) or under high crowding conditions (like in virus capsids or during ψ-condensation) DNA also shows an intrinsic ability to self-organize into large toroidal spools [7].

Micromanipulation Studies of Chromatin Fibers in Xenopus Egg Extracts Reveal ATP-dependent Chromatin Assembly Dynamics

“…The effect of an increase in bond failure force with increasing strain rate has been well documented theoretically, mainly in connection with probing of receptor-ligand interactions (Evans, 2001). This theory has been shown to describe nucleosome removal experiments (Brower-Toland et al, 2002;Pope et al, 2005), and it has been discussed in terms of the barrier associated with removal of DNA wraps by (Kulic and Schiessel, 2004). Our force-velocity curve for nucleosome disassembly (Figure 3) shows that removal of nucleosomes on shorter time scales (i.e., at larger removal rates) requires larger forces, and explains why laser tweezer experiments give nucleosome disruption forces that are much larger than those expected from thermodynamic arguments (Marko and Siggia, 1997a).…”

Unusual DNA Structures Associated With Germline Genetic Activity in Caenorhabditis elegans

“…dinucleotides face minor-groove-inward would provide a substantial free energy benefit. Such structural interactions have thus been proposed to be capable of constraining nucleosomes by impeding their ability to slide along the DNA (e.g., Flaus and Richmond 1998;Kiyama and Trifonov 2002;Kulic and Schiessel 2003). Although nucleosome mobility in vivo is likely to involve a number of biophysical modalities (Flaus and Owen-Hughes 2003), some sequence-dependent kinetic impedance of nucleosome translocation could be expected from all of these modalities.…”

Designing nucleosomal force sensors

“…The unwrapping landscape shows the well-known overall features as already predicted with sequence-independent models [20,22]: (i) The most expensive state is the fully wrapped state (L,R) = (0|0); (ii) a metastable valley for nucleosomes with a single wrap, L + R = 5; (iii) a ridge for half-flipped nucleosomes with L + R = 8; and (iv) the cheapest states, nearly unwrapped nucleosomes, L + R = 12. Nucleosomes that are put under an external tension for a short enough time will be stuck in states with L + R = 5, kinetically protected by the ridge, as has been observed recently for three other sequences [14].…”

“…This leads to a high-energy transition state, the half-flipped nucleosome, between the single-wrapped and fully unwrapped nucleosome. The energy barrier arises due to two strongly bent DNA stretches in the transition state, which lead to a barrier with a height that increases like the square-root of the applied tension [20,29]. Nucleosomes, through this force-induced strengthening, are kinetically protected against transient tension.…”

“…Most remarkably, nucleosomes can generally withstand rather high tensions without unwrapping completely. This has been explained by the combination of spool geometry and DNA stiffness [15,[20][21][22][23][24][25][26][27][28][29][30][31]. In order to completely unwrap, the nucleosome has to flip by 180 degrees around its symmetry axis.…”