What can naked DNA still show the world of biology 50 years after Watson and Crick?

27 January 2006

Vincent Coljee
Prentiss Lab, Department of Physics, Harvard

Abstract

The structure of DNA is very well described and thought by most biologists to be quite well understood, at least in principle. But not all aspects of DNA have been very well described. For example, most of the information we have about separating DNA strands comes from thermal denaturation and short oligo studies. As it turns out thermal denaturation is not the natural manner by which organisms usual separate their strands. It is becoming clear that DNA doesn't behave as an entirely predictable heteropolymer when comparing experimental results with physics models either (see references below). Most importantly, at 39 deg C the force required to separate double stranded DNA becomes less than half that which it is at 35 deg C. This difference may have significant effects on the energy required to replicate or to transcribe depending on temperature. It may also offer an explanation to the advantage of being warmblooded.

In order to investigate via which mechanisms DNA achieves this reduction in energy, we are currently focusing on single strand DNA (ssDNA). We have already discovered that ssDNA can behave very differently from physics models as well. Aspects of ssDNA that can differ include elasticity, base stacking and the ability or inability to rezip into double stranded DNA.

Based on these experimental observations, I wish to propose several biological theories as a discussion point. These involve aspects of basic biochemistry as in replication and transcription as well as the larger scope of what it may mean to living organisms.

References

C Danilowicz, Y Kafri, R S Conroy, V W Coljee, J Weeks and M. Prentiss, "Measurement of the phase diagram of DNA unzipping in the temperature-force plane", Phys Rev Letters 93:078101 2004. PubMed

C Danilowicz, V W Coljee, C Bouzigues, D K Lubensky, D R Nelson and Mara Prentiss, "DNA unzipped under a constant force exhibits multiple metastable intermediates", PNAS 100:1694-99 2003. PubMed HTML

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