Seminar – How DNA Deals with Torsional Stress

Keck Seminar

Friday, November 14, 4pm
BRC Auditorium
6500 Main, Corner of University & Main

How DNA Deals with Torsional Stress

by Lynn Zechiedrich, PhD
Professor in Molecular Virology and Microbiology, Baylor College of Medicine

Abstract

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. We collaborated with the Wah Chiu laboratory at Baylor College of Medicine, taking advantage of their 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 circles of DNA affected their three-dimensional structure, their interactions with human topoisomerase IIalpha, and their susceptibility to chemical and enzymatic probing. Molecular dynamics simulations, in collaboration with Sarah Harris (University of Leeds, U.K.), provided possible atomistic explanations for the dramatic torsional-stress-induced structural alterations from B-form that we observed.

About Dr. Zechiedrich’s Research

During our research into DNA structure and topology, our group has developed a new class of minimized circular DNA vectors called Minivector DNA. Minivector DNAs can be ordered at Twister Biotech. Containing only a promoter and open reading frame, these DNA vectors are devoid of the large size and bacterial sequences that hamper plasmid DNA as a viable non-viral gene therapy vector. We synthesize milligram quantities of Minivector DNA as small as 200 bp, and have transfected a variety of difficult human cell lines, including suspension lymphoma cells. Currently, we are exploring the use of Minivector DNA as an expression vector for gene replacement in cell culture and animal models for human genetic diseases.

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