Unveiling the Mystery of DNA overstretching transitions
Xinghua Zhang, Hu Chen, Hongxia Fu, Patrick Doyle, and Jie Yan
When subjected to force at about 65 picoNewtons, DNA undergoes a perplexing structural
transition. Referred to as overstretching, this transition abruptly extends the contour length of
B-DNA around 1.7 times. Conflicting experimental findings have led to uncertainty about
whether this overstretching produces a single-stranded DNA or S-DNA, a novel doublestranded DNA.
In a series of publications1-2, A/P Yan Jie and his team recently made several significant
breakthroughs in resolving this debate, confirming the existence of S-DNA. They
demonstrated that the overstretching transition produces both types of structural
reorganization, depending on minor changes in the physiological environmental conditions.
In their most recent work with collaboration with Patrick Doyle from MIT and SingaporeMIT Alliance for Research and Technology, the team reported the first simultaneous
determination of the entropy and enthalpy changes pertaining to these respective types of
structural reorganization at extremely high resolution3.
Their results reveal that the transition to the S-DNA has a small negative entropy change,
distinguishing itself from the transition to single-stranded DNA that has a large positive
entropy change expected from dissociation of
the two DNA strands. The small negative
change in the transition to the S-DNA
suggests that the S-DNA is a double-stranded,
highly ordered structure. They also show that
the selection between the two transitions
depends on DNA base pair stability and can
be illustrated by a multidimensional phase
diagram. In addition to resolving the 16-year
of scientific controversy, their results provide
important insights to the structure of the
mysterious double-stranded S-DNA.
Publications:
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,