Investigating the Role of Dyskerin in DNA Damage Repair
Date
2023-03-16
Authors
Rodd, Andrew
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Abstract
Dyskerin is an RNA binding protein involved in RNA modification and telomere biology. Point mutations in Dyskerin cause diseases and are linked to cancer. These mutations are associated with high levels of genomic instability. This suggests that Dyskerin may be involved in DNA damage repair. Saccharomyces cerevisiae (yeast) has a conserved homolog of Dyskerin called Cbf5. We can use yeast to study the role of Dyskerin/Cbf5 in DNA damage repair. Disease and cancer relevant mutations found in Dyskerin were modeled onto Cbf5. The mutations R35K and D65A showed a DNA damage sensitive phenotype. This indicates that Cbf5/Dyskerin is involved in DNA damage repair. Next, the recruitment of Cbf5 to a DNA double stranded (DNAds) break site was tested using chromatin immunoprecipitation. Wild-type Cbf5 showed recruitment to a DNAds break site. This was also seen with both R35K and D65A mutants. The localization of Cbf5 supports its role in repair. The recruitment of the mutants was not impaired, showing that their sensitivity to damage may be for a different reason. Future research will investigate the function of Dyskerin at DNAds break sites and reasons why the R35K and D65A mutants are sensitive to damage.
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Cbf5, Genome Instability, Double Stranded Break Repair, DNA Damage Repair, Dyskerin