Reagent list. Reagents used in this study.

<div> Aneuploidy typically poses challenges for cell survival and growth. However, recent studies have identified exceptions where aneuploidy is beneficial for cells with mutations in certain regulatory genes. Our research reveals that cells lacking the spindle checkpoint gene <i>BUB3</i> exhibit aneuploidy of select chromosomes. While the spindle checkpoint is not essential in budding yeast, the loss of <i>BUB3</i> and <i>BUB1</i> increases the probability of chromosome missegregation compared to wildtype cells. Contrary to the prevailing assumption that the aneuploid cells would be outcompeted due to growth defects, our findings demonstrate that <i>bub3</i>Δ cells consistently maintained aneuploidy of specific chromosomes over many generations. We investigated whether the persistence of these additional chromosomes in <i>bub3</i>Δ cells resulted from the beneficial elevated expression of certain genes, or mere tolerance. We identified several genes involved in chromosome segregation and cell cycle regulation that confer an advantage to Bub3-depleted cells. Overall, our results suggest that the gain of specific genes through aneuploidy may provide a survival advantage to strains with poor chromosome segregation fidelity. </div>