Genetic code unravelled by force
How is DNA processed and read in living organisms? Researchers from the LaserLaB at the VU University Amsterdam have grabbed hold of DNA molecules and placed these under mechanical tension in an effort to answer this question. The results reveal that as the force used to pull on the DNA increases, the two DNA strands stretch, unwind and eventually separate. DNA is very stable, so the proteins must force an opening to intervene at precise locations on the DNA molecule. The international team of researchers (Dutch, French and Danish) led by FOM workgroup leaders and Vici laureates Prof. Gijs Wuite and Dr. Erwin Peterman published their results this week in the leading journal Nature Physics.
Stability versus accessibility
DNA is a large and very long molecule with a double helix shape. The genetic code is concealed between the two intertwined strands. There is a tension between keeping the strands together so that the genetic code remains safe and the need to continually read off and copy the genetic code by locally unwinding and separating the two strands. We know that increasing the temperature to about 70°C can cause the strands to unwind and separate. However, that is not how the proteins responsible for reading off and copying the DNA work. To gain a better idea of how these proteins do work, the researchers locally destabilised the DNA's structure to produce a quantitative description of the double helix's stability.
Unique unwinding process
Advanced physics techniques such as 'optical tweezers' can be used to extract a single DNA molecule and simultaneously measure its elasticity. The researchers from Amsterdam demonstrated that they could unwind the two DNA strands if they pulled hard enough on the DNA. However, they observed surprisingly complex behaviour during this process: the unwinding happened in pulses. The resultant unwinding pattern was highly specific for the DNA's underlying genetic code, a sort of fingerprint. Based on this discovery the researchers have produced a quantitative model that describes the mechanical stability of DNA with considerable accuracy.
Elasticity of DNA
The model also required an exact description of DNA's elastic properties. The standard description was inadequate, so the researchers expanded this. Including the DNA's helical shape proved to be a crucial factor; when the DNA was pulled, it is initially wound up a bit further before unwinding again at higher forces. The researchers conclude that DNA's double helix structure is highly stable and that the proteins must intervene at very precise locations on the molecule to force an opening.
Reference
'Quantifying how DNA stretches, melts and changes twist under tension', Peter Gross, Niels Laurens, Lene Oddershede, Ulrich Bockelmann, Erwin Peterman and Gijs Wuite.
Contact
Prof. G. (Gijs) Wuite +31 (0)20 598 79 87
Dr. E. (Erwin) Peterman +31 (0)20 598 75 76
Further information
http://www.nat.vu.nl/en/research/physics-life-health/single-molecule-cell-level-biophysics/index.asp