Fluorescence Imaging of Mitochondrial DNA Base Excision Repair Reveals Dynamics of Oxidative Stress Responses
Dr. Yong Woong Jun
Department of Chemistry, ChEM-H Institute, and Stanford Cancer Institute, Stanford University, Stanford, CA, 94305 USA
Search for more papers by this authorEddy Albarran
Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Wu Tsai Neuroscience institute, Stanford University School of Medicine, Stanford, CA, 94305 USA
Search for more papers by this authorDr. David L. Wilson
Department of Chemistry, ChEM-H Institute, and Stanford Cancer Institute, Stanford University, Stanford, CA, 94305 USA
Search for more papers by this authorProf. Dr. Jun Ding
Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Wu Tsai Neuroscience institute, Stanford University School of Medicine, Stanford, CA, 94305 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Eric T. Kool
Department of Chemistry, ChEM-H Institute, and Stanford Cancer Institute, Stanford University, Stanford, CA, 94305 USA
Search for more papers by this authorDr. Yong Woong Jun
Department of Chemistry, ChEM-H Institute, and Stanford Cancer Institute, Stanford University, Stanford, CA, 94305 USA
Search for more papers by this authorEddy Albarran
Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Wu Tsai Neuroscience institute, Stanford University School of Medicine, Stanford, CA, 94305 USA
Search for more papers by this authorDr. David L. Wilson
Department of Chemistry, ChEM-H Institute, and Stanford Cancer Institute, Stanford University, Stanford, CA, 94305 USA
Search for more papers by this authorProf. Dr. Jun Ding
Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Wu Tsai Neuroscience institute, Stanford University School of Medicine, Stanford, CA, 94305 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Eric T. Kool
Department of Chemistry, ChEM-H Institute, and Stanford Cancer Institute, Stanford University, Stanford, CA, 94305 USA
Search for more papers by this authorAbstract
Mitochondrial function in cells declines with aging and with neurodegeneration, due in large part to accumulated mutations in mitochondrial DNA (mtDNA) that arise from deficient DNA repair. However, measuring this repair activity is challenging. We employ a molecular approach for visualizing mitochondrial base excision repair (BER) activity in situ by use of a fluorescent probe (UBER) that reacts rapidly with AP sites resulting from BER activity. Administering the probe to cultured cells revealed signals that were localized to mitochondria, enabling selective observation of mtDNA BER intermediates. The probe showed elevated DNA repair activity under oxidative stress, and responded to suppression of glycosylase activity. Furthermore, the probe illuminated the time lag between the initiation of oxidative stress and the initial step of BER. Absence of MTH1 in cells resulted in elevated demand for BER activity upon extended oxidative stress, while the absence of OGG1 activity limited glycosylation capacity.
Conflict of interest
The authors declare no conflict of interest.
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