Computer Modeling of Dna Unknotting by Type Ii Topoisomerases

Type II topoisomerases (Topo II) are essential enzymes common to all organisms. Their cellular functions include maintaining the levels of chromosome supercoiling and ensuring proper segregation at cell division. Topo II performs strand passage on its substrate DNA. This action has been well characterized at the molecular level [2]. Topo II binds a dsDNA segment called the G-segment, it introduces a double strand break on the G-segment allowing the passage of another DNA fragment called the T-segment. When the break is resealed, both T and G segments are released. When acting on knotted DNA molecules, Topo II is known to unknot DNA below thermodynamic equilibrium [3]. That is, the steady-state fraction of knotted molecules produced by Topo II is much lower that that obtained by random cyclization of linear DNA (which depends only on the conformations adopted by DNA in solution) [3]. Different biophysical models have been proposed to explain this phenomenon [4, 5, 6].