Mitochondrial DNA Repair Processes In Oxidative Stress And Aging

$622,523ZIAFY2021AGNIH

National Institute On Aging

Investigators

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Abstract

Mitochondrial dysfunction is recognized as an important contributing factor for aging and age-related degeneration. We and others are investigating the relationship between nuclear DNA damage and mitochondrial dysfunction. Like the nuclear compartment, mitochondria have their own DNA repair and stress response systems. Previously, we reported the unexpected finding that DNA polymerase Beta (PolB) was present in mitochondria and could contribute to DNA repair in that compartment. Upon further investigation, we compared PolB and Polymerase Gamma (PolG), the replicative polymerase for mitochondrial DNA, on DNA repair substrates and intermediates. We reported that DNA PolB was more proficient at single-nucleotide gap filling and extracts lacking PolB are severely deficient in processing BER intermediates. Moving forward, we are investigating how DNA repair deficiencies contributes to altered nucleus-to-mitochondria signaling and mitochondrial dysfunction is being studied.

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