Abstract:
:Topoisomerase II (Top2) removes topological linkages between replicated chromosomes. Top2 inhibition leads to mitotic catastrophe (MC) when cells unsuccessfully try to split their genetic material between the two daughter cells. Herein, we have characterized the fate of these daughter cells in the budding yeast. Clonogenic and microcolony experiments, in combination with vital and apoptotic stains, showed that 75% of daughter cells become senescent in the short term; they are unable to divide but remain alive. Decline in cell vitality then occurred, yet slowly, uncoordinatedly when comparing pairs of daughters, and independently of the cell death mediator Mca1/Yca1. Furthermore, we showed that senescence can be modulated by ploidy, suggesting that gross chromosome imbalances during segregation may account for this phenotype. Indeed, we found that diploid long-term survivors of the MC are prone to genomic imbalances such as trisomies, uniparental disomies and terminal loss of heterozygosity (LOH), the latter affecting the longest chromosome arms.
journal_name
Aging (Albany NY)journal_title
Agingauthors
Ramos-Pérez C,Dominska M,Anaissi-Afonso L,Cazorla-Rivero S,Quevedo O,Lorenzo-Castrillejo I,Petes TD,Machín Fdoi
10.18632/aging.102573subject
Has Abstractpub_date
2019-12-08 00:00:00pages
11686-11721issue
23issn
1945-4589pii
102573journal_volume
11pub_type
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