Research Paper Volume 11, Issue 23 pp 11686—11721

Figure 6. Summary of the top2-mediated mitotic catastrophe and the fate of the immediate progeny. After inactivation of Top2, cells cannot resolve sister chromatids in anaphase, leading to an anaphase bridge between the mother (M) and its daughter (D1). These bridges are quickly severed (at least in the top2-5 mutant [25]). The immediate progeny coming from the top2 mitotic catastrophes (MCs) is largely unable to enter a new cell cycle (do not re-bud) despite remaining metabolically active for many hours; hence, these cells become senescent. Only ~25% of the original mothers re-bud once (D2) after the top2 MC. The long-term fate of most daughter cells is death. They will eventually die through accidental cell death (ACD), as deduced from both the asynchrony and asymmetry of death events and the lack of regulation by the death modulator Yca1(Mca1). The inability to enter a new cell cycle is likely a consequence of both the massive DNA damage as a consequence of bridge severing, and the misdistribution of essential genetic material coded on the chromosome arms between the daughter cells. A small proportion of the progeny, especially those cell that underwent a milder top2 MC (e.g., already in S/G₂ at the time of Top2 inactivation) survives to yield a population of cells with characteristic footprints of genomic instability. Two of these footprints, terminal loss of heterozygosity (T-LOH) and uniparental disomy (UPD) are expected outcomes from anaphase bridges.