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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • December 8, 2019

Published In

Volume / Issue

  • 11 / 23

Start / End Page

  • 11686 - 11721

PubMed ID

  • 31812950

Pubmed Central ID

  • PMC6932922

Electronic International Standard Serial Number (EISSN)

  • 1945-4589

Digital Object Identifier (DOI)

  • 10.18632/aging.102573

Language

  • eng

Conference Location

  • United States