BPS2026 – Stress associated with genome imbalance

Aneuploidy, a consequence of improper segregation of chromosomes during mitosis and meiosis, is a large-effect genetic alteration that can cause both selectable phenotypic variation and cellular stress. Our previous work in yeast demonstrated that a common cellular stress caused by diverse aneuploid chromosome stoichiometries is hypo-osmotic-like stress, likely resulting from proteome imbalance. Our recent study investigated biophysical changes associated with aneuploidy in human cells and revealed similar stress characteristics. Interestingly, we found that hypo-osmotic stress in turn affects mitotic fidelity and predispose cells to chromosome instability and aneuploidy. We propose that the interplay between osmotic stress and chromosome instability may be a potent driver of cancer evolution under chronic inflammatory conditions.