Metabolism-induced genome instability in polyploid Candida albicans cells

Thomson, Gregory

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Overview

Year:: 2020
Contributor:: Thomson, Gregory (creator); Bennett, Richard (Advisor); Johnson, Mark (Reader); Vaishnava, Shipra (Reader); Belenky, Peter (Reader); Lin, Xiaorong (Reader); Brown University. Department of Molecular Biology, Cell Biology and Biochemistry (sponsor)
Genre:: theses
Subject:: Metabolism; Candida albicans; Polyploidy; Genome Instability
Extent:: xvi, 207 p.

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Description

Abstract:: Understanding how cellular activities impact genome stability is critical to multiple biological processes including tumorigenesis and reproductive biology. The fungal pathogen Candida albicans displays striking genome dynamics during its parasexual cycle as tetraploid cells, but not diploid cells, exhibit genome instability and reduce their ploidy when grown on a glucose-rich ‘pre-sporulation’ medium. Here, we reveal that C. albicans tetraploid cells are metabolically hyperactive on this medium with higher rates of fermentation and oxidative respiration relative to diploid cells. This heightened metabolism results in elevated levels of reactive oxygen species (ROS), activation of the ROS-responsive transcription factor Cap1, and the formation of DNA double-strand breaks. Genetic or chemical suppression of ROS levels suppresses each of these phenotypes and also protects against genome instability. These studies reveal how endogenous metabolic processes can generate sufficient ROS to trigger genome instability in polyploid C. albicans cells. We also discuss potential parallels with metabolism-induced instability in cancer cells and speculate that ROS-induced DNA damage could have facilitated ploidy cycling prior to a conventional meiosis in eukaryotes.
Notes:: Thesis (Ph. D.)--Brown University, 2020

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Rights: In Copyright
Restrictions on Use: Collection is open for research.

Citation

Thomson, Gregory, "Metabolism-induced genome instability in polyploid Candida albicans cells" (2020). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:1129368/

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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations

Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department.
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