NUS researchers revealed three distinct structural reorganizations of DNA by mechanical
stretching
In addition to storing the genetic information of cells, double-stranded DNA (dsDNA) performs
multiple functions that require different DNA structural reorganizations. Recent single-molecule
studies revealed that mechanical stretching could induce DNA structural transitions that elongate
DNA backbone. Yet, the nature of the transitions has not been fully understood. For torsionunconstrained DNA, only three possible structural transitions may exist: (i) “peeling” apart of one
ssDNA strand from the other (1ssDNA), (ii) “inside-strand separation” of dsDNA to two parallel
ssDNA strands (2ssDNA), and (iii) producing a novel base-paired dsDNA structure, termed “S-DNA”.
These possibilities have been discussed and which ones do exist has been heavily debated for 17 years.
In a series of recent studies led by Jie Yan (Associate Professor of Department of Physics, Principal
Investigator of Mechanobiology Institute (MBI), Centre of Bio-imaging Sciences (CBIS), and
Singapore-MIT Alliance for Research and Technology (SMART)) demonstrated that all the three
transitions exist, and which ones occur depends on experimental conditions. The resulting three
distinct DNA structures are fully characterized for their respective mechanical and thermodynamic
properties (1-4). In particular, in their newest study in collaboration with Patrick Doyle (MIT
Investigator of SMART), which is published in PNAS back-to-back with another study by King et al.
(5), the existence of the S-DNA was unambiguously demonstrated and the “inside-strand-separation”
of dsDNA was observed and characterized for the first time.
These results provide a full understanding of force-driven structural transitions of torsionunconstrained DNA.
References
1. Fu, H., Chen, H., Marko, J.F. and Yan, J. Two distinct overstretched states. Nucleic Acids
Research, 2010, 38, 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, 109,
8103-8108.
4. Zhang, X., Chen, H., Le S., Rouzina I., Doyle, P. S., and Yan, J. Revealing the competition
between peeled ssDNA, melting bubbles, and S-DNA during DNA overstretching by singlemolecule calorimetry. PNAS, Advanced Access (doi:10.1073/pnas.1213740110)
5. King G. A. , et al. Revealing the competition between peeled ssDNA, melting bubbles, and
S-DNA during DNA overstretching using fluorescence microscopy. PNAS, Advanced Access
(doi: 10.1073/pnas.1213676110).