Metabolism-induced oxidative stress and DNA damage selectively trigger genome instability in polyploid fungal cells.

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 chemic

SUBMITTER: Thomson GJ 

PROVIDER: S-EPMC6769381 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature