How DNA deals with torsional stress
Sixty years after Watson and Crick elucidated its B-form structure, amazing facts about DNA continue to emerge as tools to study it become increasingly sophisticated. At Baylor College of Medicine, we collaborate with the Wah Chiu laboratory, taking advantage of state-of-the-art cryo-electron tomography facilities, to determine the three-dimensional structures of biologically active DNA. We determined how underwinding or overwinding tiny (336 bp) circles of DNA affected their three-dimensional structure, their interactions and activity with human topoisomerase II, and their susceptibility to chemical and enzymatic probing. Molecular dynamics simulations, in collaboration with Sarah Harris (University of Leeds, U.K.), provide possible atomistic explanations for the dramatic torsional-stress-induced structural alterations from B-form that we observe. In summary, non-linear structural deviations of DNA drive DNA activity and we must re-write the text book on the structure of active DNA.
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