Studies on the Mechanisms of DNA Damage Repair in Human Neurons
Abstract: Many studies suggest that DNA lesions are increased in aging cells. Although repairing the lesion in DNA is critical for proper cellular function, it has not been fully understood how neurons cope with various DNA lesions, especially in aging brain. In particular, most of neurons in the brain are irreplaceable with new cells unlike majority of cells in other tissues and organs and the failure of DNA repair in neurons may lead to neurodegenerative diseases including Alzheimer’s disease. To investigate DNA repair activities in neurons, we first assessed the expression of various DNA repair genes in aging neurons as well as other cell types as controls. We collected gene expression profile data from Genotype-Tissue Expression (GTEx) consortium that contain 11,688 RNA-Seq samples (RNA samples obtained from 53 different tissues of 635 individuals with ages range from 20s to 80s). We found sets of genes involved in mismatch repair and homologous repair pathways those expressions are positively or negatively correlated to the age. To investigate the effect of altered expression of these genes in DNA repair and neuronal function, we are developing a new model system using induced pluripotent stem cells.
Sai Sree Sumitra Kalagara*
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