Welcome to the Doetsch Laboratory!
Major areas of research focus in this laboratory are (1) the biochemistry, molecular biology and genetics of DNA repair and its regulation; (2) the interaction of the transcriptional machinery with DNA damage; (3) and elucidation of the mechanisms of action of DNA targeting anticancer agents, including ionizing radiation.
Our DNA repair studies include the characterization of the repair of oxidative and ionizing radiation-induced DNA base damage in the nucleus and mitochondria. An area of emphasis is the regulation of base excision repair through a process called dynamic compartmentalization. Studies on the effects of various types of DNA damage on RNA polymerases have led to the discovery of transcriptional mutagenesis (TM) and current studies are focused on defining its occurrence and consequences in bacterial and mammalian systems. Particular emphasis in these studies is the role of TM in the acquisition of drug resistance in microbial pathogens and in tumor development in mammalian systems. Studies on DNA damage management systems have led to several current projects investigating DNA damage-induced cellular responses involving the production of reactive oxygen species (ROS) as a stress signaling molecule. These studies include the ROS responses following cellular exposure to both low and high LET ionizing radiation and to chemotherapeutic agents such as cisplatin. Defining these responses has provided novel insights into the biological endpoints of radiation exposures as well as the mechanism of action of antitumor agents.