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Hello and welcome to the home page for the Dr. Mark Muller’s Laboratory of Cancer Research at the University of Central Florida in beautiful Orlando, Florida. The laboratory is an established group of researchers working on the molecular biology of cancer and gene regulation. Specific research focus areas include studies on DNA topoisomerases, gene silencing, DNA repair and telomerase regulation. For details go to research.
Latest News from the lab: Dr. Muller returned from an 8 month sabbatical in Naples, Italy working with collaborators (Professor Enrico Avvedimento, Antonio Porcellin) on gene silencing mechanisms following repair. This work was recently published (see GADD45 paper in Nuc. Acid. Res. below).
Welcome Dr. Orde Munro, from the University of Kwazulu-Natal (Pietermaritzburg, South Africa). Dr. Munro is an inorganic chemist and his group has synthesized a large number of new gold compounds that target pro- and eukaryotic topoisomerases. He is here on a Fullbright Fellowship for 2010-11.
Congratulations to Vidusha Cyril, who just defended here thesis in November 2011.
Recently Published:
GADD45a inhibition of DNMT1 dependent DNA methylation during homology directed DNA repair Bongyong Lee; Annalisa Morano; Antonio Porcellini; Mark T. Muller Nucleic Acids Research 2011; doi: 10.1093/nar/gkr1115
Full Text: http://nar.oxfordjournals.org/cgi/content/full/gkr1115? ijkey=ZUGWyeMA3Y6RDY4&keytype=ref
PDF: http://nar.oxfordjournals.org/cgi/reprint/gkr1115? ijkey=ZUGWyeMA3Y6RDY4&keytype=ref
Synopsis: Gadd45a is a DNA damage inducible protein. We report that homologous recombination (HR) strongly induces Gadd45a expression which interacts with the methylase machinery and alters the expression status of the HR segments. Additionally, we propose that Gadd45a may act as a barrier to spreading of silenced chromatin to contiguouos regions.
Under Revision.
Cyril, V. and Muller, M. A Solid Phase Assay for Topoisomerase I Interfacial Poisons and Catalytic Inhibitors. Analytical Biochemistry. (2012)
ABSTRACT
We report a mechanism based screening technique to rapidly identify eukaryotic topoisomerase I targeting agents. The method is based on genetic tagging of topoisomerase I to immobilize the enzyme on a solid surface in a microtiter well format. DNA is added to the wells and retained DNA is detected by Picogreen fluorescence. Compounds that result in an increase in Picogreen staining represent potential topoisomerase interfacial poisons while those that reduce fluorescence report catalytic inhibitors; therefore, the solid phase assay represents a ‘bimodal’ readout that reveals mechanisms of action. The method has been demonstrated to work with known interfacial poisons and catalytic inhibitors. This method is rapid, robust, economical and scalable for large library screens.
Submitted for Publication
Baek, S., Lee, J., Khadka, P, Muller, M and Chung, I. (2012) P53 Modulates telomerase activity through MKRN1 Ubiquitin Ligase. Submitted for publication,
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