Mitochondrial DNA Repair Processes In Oxidative Stress And Aging

线粒体功能障碍被认为是导致衰老和老年性退行性变的重要因素。我们和其他人正在研究核DNA损伤和线粒体功能障碍之间的关系。与核室一样，线粒体也有自己的DNA修复和应激反应系统。 此前，我们报道了一项出人意料的发现，DNA聚合酶Beta(PolB)存在于线粒体中，可能有助于线粒体中的DNA修复。在进一步的研究中，我们比较了PolB和复制线粒体DNA的聚合酶(Polg)在DNA修复底物和中间体上的差异。我们报道了DNA PolB更擅长单核苷酸缺口填充，而缺乏PolB的提取物在处理BER中间体方面严重不足。展望未来，我们正在研究DNA修复缺陷如何导致核到线粒体信号的改变，以及线粒体功能障碍的研究。

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.