Anyone who has been on a sailing boat knows that tying a knot is the best way to secure a rope to a hook and prevent its slippage. The same applies to sewing threads where knots are introduced to prevent them slipping through two pieces of fabric. How, then, can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of various biological systems? This is the fascinating question addressed by Dr. Antonio Suma and Dr. Cristian Micheletti, researchers at the International School for Advanced Studies (Scuola Internazionale Superiore di Studi Avanzati or SISSA) in Trieste, Italy, who used computer simulations to investigate the options available to the genetic material in such situations. The study was published online on March 28, 2017 in PNAS. The article is titled “Pore Translocation of Knotted DNA Rings.” "Our computational study sheds light on the latest experimental breakthroughs on knotted DNA manipulation and adds interesting and unexpected elements," explains Dr. Micheletti. "We first observed how knotted DNA filaments pass through minuscule pores with diameter of about 10 nanometers (10 billionths of a meter). The behavior observed in our simulations was in good agreement with the experimental measurements obtained by an international research team led by Dr. Cees Dekker, which were published only a few months ago in Nature Biotechnology. These advanced and sophisticated experiments marked a turning point for understanding DNA knotting. However, current experiments cannot ‘see’ how DNA knots actually pass through the narrow pore. In fact, the phenomenon occurs over a tiny spatial scale, and is therefore inaccessible to microscopes.
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