Novel DNA molecules designed and synthesized to study DNA topology and topoisomerases.

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ImageA research team led by Prof. Fenfei Leng in the Biomolecular Sciences Institute (BSI) and Department of Chemistry and Biochemistry has recently synthesized a type of novel fluorescently labeled circular DNA molecules to study DNA topology and topoisomerases by fluorescence resonance energy transfer (FRET). Since fluorescence intensity of these DNA molecules is dependent on supercoiling status, they are powerful tools to study DNA topology and topoisomerases. Because only a few nano grams of these fluorescently labeled circular DNA molecules are needed for 384-well or 1536-well plates for detection, these DNA molecules cab be used to develop rapid and efficient high-throughput screening (HTS) assays to identify inhibitors from the millions of compounds found in small molecule libraries that may target DNA topoisomerases, such as bacterial DNA gyrase and human DNA topoisomerase I & II (bacterial DNA gyrase inhibitors, such as ciprofloxacin are antibiotics and human topoisomerase inhibitors such as camptothecin and doxorubicin are potent anticancer drugs). Although DNA topoisomerases are important drug targets, automatic HTS screening of small molecule libraries for DNA topoisomerases has not been performed yet. The availability of fluorescence-labeled DNA molecules described in this manuscript will greatly facilitate the HTS screening of small compound libraries and should lead to discover new anticancer and antibacterial compounds in the future. The research article entitled “Fluorescently labeled circular DNA molecules for DNA topology and topoisomerases” and authored by Maxwell Gu, Andrea Berrido, Walter G. Gonzalez, Jaroslava Miksovska, Jeremy W. Chambers & Fenfei Leng (corresponding author) is published at Scientific Reports (http:/www.nature.comarticles/srep36006) on October 31, 2016. The first author, Maxwell Gu, is a high school senior at American Heritage School, Plantation, FL.