Cytological and genetic consequences for the progeny of a mitotic catastrophe provoked by Topoisomerase II deficiency.

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

Aging

authors

Ramos-Pérez C,Dominska M,Anaissi-Afonso L,Cazorla-Rivero S,Quevedo O,Lorenzo-Castrillejo I,Petes TD,Machín F

doi

10.18632/aging.102573

subject

Has Abstract

pub_date

2019-12-08 00:00:00

pages

11686-11721

issue

23

issn

1945-4589

pii

102573

journal_volume

11

pub_type

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