Presentation Type

Poster

Start Date

5-8-2024 11:00 AM

End Date

5-8-2024 1:00 PM

Subjects

DNA Damage and DNA Replication

Advisor

Jason Podrabsky

Student Level

Doctoral

Abstract

Timely and faithful replication of the genome is a requirement for cell survival and proliferation, with errors in this process leading to cancers and cell death. DNA replication during exposure to stressful conditions can lead to increased mutational burden, with collapsed replication forks causing mutations leading to cancers due to loss of repair capabilities during these exposures. Learning how stressful DNA replication takes places can lead to a better understanding of how resistant cancers survive similar conditions, like hypoxic tumor microenvironment, direct irradiation, and DNA damaging chemotherapeutics. Using an extremophile model, Austrofundulus limnaeus, which can survive these genotoxic stressors could provide valuable insights. Previous work has shown that the annual killifish can withstand high levels of DNA damage and continue DNA replication through this damage. Through QIBC I hoped to elucidate the mechanisms used to replicate through this damage. High activity of ATR during anoxia and recovery suggests that active maintenance of replication forks is occurring during anoxic exposure, and through continued work I hope to determine if the annual killifish can maintain strict control of replication and repair seen to be lost in other organisms during stressful conditions.

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May 8th, 11:00 AM May 8th, 1:00 PM

Improved Genome Maintenance and DNA Replication in the Anoxia Tolerant Annual Killifish

Timely and faithful replication of the genome is a requirement for cell survival and proliferation, with errors in this process leading to cancers and cell death. DNA replication during exposure to stressful conditions can lead to increased mutational burden, with collapsed replication forks causing mutations leading to cancers due to loss of repair capabilities during these exposures. Learning how stressful DNA replication takes places can lead to a better understanding of how resistant cancers survive similar conditions, like hypoxic tumor microenvironment, direct irradiation, and DNA damaging chemotherapeutics. Using an extremophile model, Austrofundulus limnaeus, which can survive these genotoxic stressors could provide valuable insights. Previous work has shown that the annual killifish can withstand high levels of DNA damage and continue DNA replication through this damage. Through QIBC I hoped to elucidate the mechanisms used to replicate through this damage. High activity of ATR during anoxia and recovery suggests that active maintenance of replication forks is occurring during anoxic exposure, and through continued work I hope to determine if the annual killifish can maintain strict control of replication and repair seen to be lost in other organisms during stressful conditions.