A new material constant of DNA is the major determinant of looping dynamics

DNA bending and looping is crucial for gene expression, packaging, and chromatin organization. While the static flexibility of DNA is well-characterised by the bending elasticity or persistence length, no equivalent quantity related to how quickly it responds to external mechanical or thermal forces has to date been characterised. Here, by analysing the single molecule fluctuations of DNA several kilobases long, and by developing new theory for bending dissipation in semiflexible polymers, we show that DNA bending dynamics cannot be explained by friction between DNA and the solvent alone and requires significant contribution of intramolecular DNA friction. This defines a new material constant of DNA — the bending friction constant — which we determined to be ζ _B = 241 ± 17 µ g nm ³ /ms. This magnitude corresponds to bending friction dominating dynamics of short DNA — up to ≈ 420nm or 1.24kbp — and a characteristic persistence time of DNA shapes of ≈ 1.2ms. Using these values, our theory accurately predicts measured spontaneous looping times without any fitting parameters in stark contrast to the prevailing theory based only on solvent friction with DNA, which underestimates these times by 1,000-fold. Our measurement of DNA bending friction is also insensitive to changes in electrostatic screening suggesting that it is related to the local and complex energy barriers due to Watson-Crick base-pairs, base-stacking and their interaction with water molecules as DNA bends; this localised nature suggests an opportunity for biology to use specific sequence motifs to tailor the friction response of DNA. These findings change our understanding of DNA bending dynamics and highlight the nature of the fundamental trade-off between the speed limit for DNA bending by spontaneous fluctuations, versus the energy cost of manipulating DNA by enzymes, as necessitated by biological function and ultimately, natural selection.