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.
Highlights
Mitotic catastrophe (MC) is a class of cell death still poorly understood, and with a conflictive definition among the scientific community [1,2,3]
We have recently reported that the top2-5 thermosensitive mutant undergoes timely progression through the cell cycle until a mitotic catastrophe (MC) occurs in late anaphase [25]
We have studied the consequences of inactivating Top2 in yeast through the top2-5 thermosensitive allele
Summary
Mitotic catastrophe (MC) is a class of cell death still poorly understood, and with a conflictive definition among the scientific community [1,2,3]. MC is presumed to be of the utmost importance in cancer biology, both as an oncosuppressive barrier in carcinogenesis and as a mechanism of cell death after anti-cancer treatments. Many antitumor drugs that damage the DNA or the microtubules lead to chromosome segregation failures, provided that cells do not stop their division cycle in a timely fashion [4, 5]. Human cells make use of checkpoints to arrest the cell cycle in G1/S or G2/M following treatment with these antitumor drugs, and tumour cells frequently lack one or several of these checkpoints. Cancer cells often die after a transient cell cycle arrest through a regulated cell death (RCD) known as intrinsic apoptosis [6]. When www.aging-us.com checkpoints or apoptosis are non-functional, MC is expected to ensue. Understanding MC is becoming increasingly important in cancer biology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
