Jie Yan publishes novel findings on DNA stretching in PNAS

MBI’s Associate Prof Jie Yan publishes novel findings on DNA stretching in the Proceedings of the National Academy of Sciences (PNAS)

A phase diagram showing the transition boundaries between B-DNA and single stranded DNA (coloured solid lines), B-DNA and S-DNA (grey solid line) and S-DNA and single stranded DNA (coloured dashed lines).

Research led by A/P Yan, prinicipal investigator at MBI and the Department of Physics, NUS, reveals the intricacies of DNA mechanics using highly sensitive single molecule manipulations in combination with bioimaging. Latest findings from the Yan lab, published in PNAS, reveal how DNA undergoes a perplexing structural transition when subjected to small forces. This transition, termed overstretching, has been a topic for debate for many years due to the uncertainty over precisely what structural changes result from it. Work from the Yan lab finally sheds some light on the conflicting experimental findings in this field.

Stretching DNA

A/P Yan studies how B-DNA, the predominant form of DNA found in living organisms, changes in structure in response to force. Overstretching of DNA has in some experimental set ups been shown to transform B-DNA into single-stranded DNA, whilst in others has been shown to produce a novel form of double-stranded DNA termed S-DNA. Results from the Yan lab show that overstretching does in fact bring about both of these conformations depending on minor changes in the physiological environment [1,2].

The Jie lab took B-DNA attached to a paramagnetic bead and using a magnetic field overstretched it to form two new DNA structures; S-DNA and single-stranded DNA.

New Insights from Thermodynamics

In collaboration with A/P Patrick Doyle from the Singapore-MIT Alliance for Research and Technology, A/P Yan and colleagues now report the first simultaneous determination of the entropy and enthalpy changes that occur during DNA overstretching to bring about these two new conformations [3]. High resolution measurements of the thermodynamic changes that occur during these conformational changes highlighted key differences during the production of S-DNA versus single-stranded DNA.

The transition from B-DNA to single stranded DNA was associated with a large positive entropy, which was expected in order to separate the two strands of DNA. In contrast the transition from B-DNA to S-DNA results in a small negative entropy, suggesting firstly that S-DNA is double-stranded and secondly that it is a highly ordered structure.

These findings bring clarity to 16 years of scientific debate over the conformational changes resulting from DNA overstretching and also lay the foundations for further research into what these changes may mean in vivo.

1. Fu, H., Chen, H., Marko, J.F. and Yan, J. Two distinct overstretched states. Nucleic Acids Research, 2010, 38(16), 5594-5600.

2. Fu, H., Chen, H., Zhang, X., Qu, Y., Marko, J.F. and Yan, J. Transition dynamics and selection of the distinct S-DNA and strand unpeeling modes of double helix overstretching, Nucleic Acids Research, 2011, 39, 3473-3481.

3. Zhang, X., Chen, H., Fu, H., Doyle, P. S., and Yan, J. Two distinct overstretched DNA structures revealed by single-molecule thermodynamics measurements, PNAS, 2012. In press.