The role of DNA damage and repair at telomeres

National Institute On Aging

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Abstract

We are investigating the impact of oxidized guanine and uracil on telomere integrity and the role of their repair enzymes, 8oxoguanine DNA glycosylase 1 (OGG1) and uracil DNA glycosylase (UNG) in telomere length maintenance, which are summarized as follows: (1) Impact of oxidized guanine lesions on telomeres in budding yeast and mammalian cells: We found that oxidized guanine lesions accumulated in telomeres in budding yeast and mice that were defective in OGG1 function. These base lesions led to changes in telomere length. Furthermore, the level of base lesions determined the degree of telomere length alteration. Thus, OGG1 is critical in excising telomeric oxidized guanines and plays an important role in telomere length maintenance in yeast and mammals. (2) Impact of uracil base modification on telomeres in human: We found that ablation of UNG function led to telomere attrition in human cells. These data suggest that uracil attenuates telomere integrity and that UNG plays a key role in telomeric uracil repair and telomere length maintenance in human. Our overall effort will facilitate our understanding on how base lesions may impact telomere integrity and thus aging.