Poster Sessions

Mol-3

Jian Lu

J. Lu, Y. Liu

The 8-oxoguanine DNA glycosylase (Ogg1) is required for telomere length regulation in Saccharomyces cerevisiae

Telomeres are nucleoprotein structures that protect chromosome ends from nucleolytic digestion and from being recognized as double-strand breaks. Here we utilize the budding yeast Saccharomyces cerevisiae as a model to investigate the effect of oxidative stress in telomere maintenance. Telomere sequence is rich in G, which could be oxidized to 8-oxo-7,8-dihydroguanine (8-oxoG). The OGG1 gene encodes 8-oxoguanine DNA glycosylase, which initiates the first step to repair 8-oxoG. We found that lack of Ogg1 causes telomere lengthening, which can be complemented by the wild-type OGG1 gene. Normally, telomere elongation can be achieved by telomerase, a specialized enzyme which add telomere repeats to counteract the telomere shortening. Alternatively, telomeres can be amplified via recombination when telomerase is absent. Interestingly, we showed that over-elongated telomere in the ogg1 mutant is dependent on both the telomerase and the recombination, as removal of either pathway in the ogg1 mutant abolished telomere lengthening. Furthermore, we found that the level of 8-oxoG is elevated in the telomere region in the ogg1 mutant. In vitro binding assay showed that the presence of 8-oxoG in the telomere sequence decreased the binding to the Rap1, a negative regulator of telomere length. Currently we are investigating if in vivo Rap1 binding is affected in the ogg1 mutant using chromatin immunoprecipitation assay. In summary, our results suggest that Ogg1 plays important role in telomere length regulation. Given that Ogg1 is conserved in eukaryotes, from yeast to human, it can be speculated that human Ogg1 has a similar function.