p53 Prohibits Propagation of Chromosome Segregation Errors that Produce Structural Aneuploidies

Abstract

Summary: The presence of an abnormal karyotype has been shown to be profoundly detrimental at the cellular and organismal levels but is an overt hallmark of cancer. Aneuploidy can lead to p53 activation and thereby prevents proliferation, but the exact trigger for p53 activation has remained controversial. Here, we have used a system to induce aneuploidy in untransformed human cells to explore how cells deal with different segregation errors. We show that p53 is activated only in a subset of the cells with altered chromosome content. Importantly, we find that at least a subset of whole-chromosome aneuploidies can be propagated in p53-proficient cells, indicating that aneuploidy does not always lead to activation of p53. Finally, we demonstrate that propagation of structural aneuploidies (gain or loss of part of a chromosome) induced by segregation errors is limited to p53-deficient cells. : Chromosome segregation errors can result in whole-chromosome aneuploidies or structural aneuploidies (involving only chromosome fragments). Here, Soto et al. show that whole-chromosome aneuploidies do not always lead to p53 activation and can therefore be propagated in a p53-proficient setting, whereas structural imbalances that result from segregation errors cannot. Keywords: aneuploidy, p53, chromosome missegregation, single-cell sequencing