DF/HCC Program Affiliation

Cancer Genetics

Research Abstract

Oxidative damage to DNA accumulates with age in the brain, particularly in mitochondrial DNA (mtDNA). Oxidatively DNA damage can induce point mutations. mtDNA point mutations accumulate with age in the brain, with mutation levels correlating inversely with mitochondrial function. Somatic mtDNA point mutations also accumulate within certain cancers. We are now studying the accumulation of mtDNA point mutations in single neurons in the brain using laser capture microdissection to isolate single substantia nigra neurons. In addition, we are establishing an in vitro system for assessing the functional significance of somatic mtDNA mutations, by either inhibition or overexpression of mtDNA repair enzymes that specifically repair oxidative damage to DNA. These data have potential relevance to diseases involving oxidative stress and DNA damage or repair, including aging, neurodegenerative disorders, and cancer.

Publications

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