This novel double-stranded DNA structure produced through mechanical stretching has been successfully demonstrated by researchers from the National University of Singapore. Credit: National University of Singapore

Double-stranded
DNA has often been described as a right-handed helical structure, known
as B-DNA. To perform its multiple functions, double-stranded DNA has
multiple structures depending on conditions. For example, the melted DNA
bubble forms during transcription elongation and the left-handed
helical Z-DNA forms hypothetically during transcriptional regulations.

   

Scientists
have been proposing a novel form of double-stranded DNA structure since
1996. Referred to as ‘S-DNA’, it is produced from stretching the B-form
DNA beyond a certain ‘transition force’ of around 65 pN to
approximately 1.7-fold in length (termed as DNA overstretching
transition). Its existence has sparked a 16-year scientific debate since
it was proposed, as many other evidences suggested that DNA
overstretching transition was merely a force-induced DNA melting
transition, leading to peeled-apart single-stranded DNA.

   

At National University of Singapore (NUS),
the research was led by Associate Professor Jie Yan, from the
Department of Physics, Faculty of Science and Mechanobiology Institute,
Singapore. It succeeded in demonstrating the intricacies of the DNA
mechanics in highly sensitive single-DNA stretching experiments.

   

Assoc
Prof Yan and his team found that DNA overstretching may involve two
transitions that are distinct in their transition kinetics, namely, a
slower hysteretic peeling transition to peeled-apart single-stranded DNA
and a faster non-hysteretic transition to an unknown DNA structure.
However, whether the unknown DNA structure produced from the
non-hysteretic transition is the S-DNA or two single-stranded DNA
strands through inside-DNA-melting, remains a question.

   

Their findings were published in Nucleic Acids Research.

   

In another recent work published in Proceedings of the National Academy of Sciences,
Assoc Prof Yan and co-researchers examined the thermodynamics
associated with the two transitions. They found that the non-hysteretic
transition was associated with a small negative entropy change, in
contrast to the large positive entropy change found during the
hysteretic peeling transition. This result strongly favors DNA
re-arrangement into a highly ordered, non-melted state during the
non-hyteretic transition. They also demonstrated that the selection
between the two transitions was dependent on DNA base-pair stability and
could be represented in a multi-dimensional phase diagram.

   

Their
results not only brought clarity to the scientific debate of whether
S-DNA exists, but also provided important insights to the possible
structures and functions of the mysterious S-DNA.

   

Given
its elongated structure, the S-DNA may be a potential binding substrate
for DNA intercalators, including those used in chemotherapeutic
treatment to inhibit DNA replication in rapidly growing cancer cells. In
cells, many DNA-binding proteins utilize side chain intercalation to
distort the DNA backbone. Therefore, the S-DNA may also be a potential
binding substrate for these proteins that occur in living organisms.

Source: National University of Singapore