Event Title

Wrnexo’s Role In Responding To Oxidative Stress In Drosophila Melanogaster

Location

Lobby in front of Auditorium

Start Date

19-4-2019 11:00 AM

Department

Biology

Description

DNA replication is an imperfect process that is susceptible to interference from inside as well as outside the cell. One source of interference is oxidative stress, which is the toxic buildup of free radicals. Free radicals can take electrons from DNA causing damage that can lead to mutations and cancer. To counteract these consequences and maintain genomic stability, cells have several DNA repair pathways. One defense against DNA damage is the protein WRN. In humans, WRN facilitates proper DNA replication and repair of oxidative DNA damage. Mutations in WRN cause Werner syndrome, a disease characterized by accelerated aging and an increased risk of cancer. In Drosophila melanogaster, WRNexo is homologous to WRN. WRNexo has a conserved exonuclease domain but does not have a helicase domain. This allows us to focus on the function of the exonuclease alone. A deletion in WRNexo (WRNexo ∆ ) results in deficiencies in DNA replication during the embryo and larval life stages. We investigated if WRNexo protects against DNA damage caused by oxidative stress by treating WRNexo ∆ mutants with paraquat, an herbicide that generates free radicals. Because of the importance of WRNexo in Drosophila DNA replication, we expected to see high sensitivity of WRNexo ∆ to paraquat during the larval stage when cell division is high. Surprisingly, WRNexo ∆ mutants are also not sensitive to paraquat as the relative survival of homozygous WRNexo ∆ mutants was the same as heterozygous flies. Lastly, oxidative stress can also cause lipid peroxidation, leading to membrane damage and low body fat levels. We quantified the body fat content in WRNexo ∆ by performing larval buoyancy assays in which larvae were floated in increasing concentrations of a sucrose solution; floating has been shown to correlate with high body fat. We observed less floating in WRNexo ∆ larvae, demonstrating that they had lower body fat content than that of our wild type flies. Because the low body fat suggests higher oxidative stress, we plan to further characterize oxidative stress in our mutants by treating them with additional stressors to evoke a strong response. Understanding the interactions of WRNexo in responding to oxidative stress may allow us to develop better chemotherapy drugs and may also give us further insight on cancer and aging.

Comments

Elyse Bolterstein is the faculty sponsor of this poster.

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Apr 19th, 11:00 AM

Wrnexo’s Role In Responding To Oxidative Stress In Drosophila Melanogaster

Lobby in front of Auditorium

DNA replication is an imperfect process that is susceptible to interference from inside as well as outside the cell. One source of interference is oxidative stress, which is the toxic buildup of free radicals. Free radicals can take electrons from DNA causing damage that can lead to mutations and cancer. To counteract these consequences and maintain genomic stability, cells have several DNA repair pathways. One defense against DNA damage is the protein WRN. In humans, WRN facilitates proper DNA replication and repair of oxidative DNA damage. Mutations in WRN cause Werner syndrome, a disease characterized by accelerated aging and an increased risk of cancer. In Drosophila melanogaster, WRNexo is homologous to WRN. WRNexo has a conserved exonuclease domain but does not have a helicase domain. This allows us to focus on the function of the exonuclease alone. A deletion in WRNexo (WRNexo ∆ ) results in deficiencies in DNA replication during the embryo and larval life stages. We investigated if WRNexo protects against DNA damage caused by oxidative stress by treating WRNexo ∆ mutants with paraquat, an herbicide that generates free radicals. Because of the importance of WRNexo in Drosophila DNA replication, we expected to see high sensitivity of WRNexo ∆ to paraquat during the larval stage when cell division is high. Surprisingly, WRNexo ∆ mutants are also not sensitive to paraquat as the relative survival of homozygous WRNexo ∆ mutants was the same as heterozygous flies. Lastly, oxidative stress can also cause lipid peroxidation, leading to membrane damage and low body fat levels. We quantified the body fat content in WRNexo ∆ by performing larval buoyancy assays in which larvae were floated in increasing concentrations of a sucrose solution; floating has been shown to correlate with high body fat. We observed less floating in WRNexo ∆ larvae, demonstrating that they had lower body fat content than that of our wild type flies. Because the low body fat suggests higher oxidative stress, we plan to further characterize oxidative stress in our mutants by treating them with additional stressors to evoke a strong response. Understanding the interactions of WRNexo in responding to oxidative stress may allow us to develop better chemotherapy drugs and may also give us further insight on cancer and aging.