Supplementary material from "Topoisomerase iiα prevents ultrafine anaphase bridges by two mechanisms"
Posted on 2020-05-08 - 04:53
Topoisomerase IIα (Topo IIα), a well-conserved double-stranded DNA (dsDNA)-specific decatenase, processes dsDNA catenanes resulting from DNA replication during mitosis. Topo IIα defects lead to an accumulation of ultrafine anaphase bridges (UFBs), a type of chromosome non-disjunction. Topo IIα has been reported to resolve DNA anaphase threads, possibly accounting for the increase in UFB frequency upon Topo IIα inhibition. We hypothesized that the excess UFBs might also result, at least in part, from an impairment of the prevention of UFB formation by Topo IIα. We found that Topo IIα inhibition promotes UFB formation without affecting the global disappearance of UFBs during mitosis, but leads to an aberrant UFB resolution generating DNA damage within the next G1. Moreover, we demonstrated that Topo IIα inhibition promotes the formation of two types of UFBs depending on cell cycle phase. Topo IIα inhibition during S-phase compromises complete DNA replication, leading to the formation of UFB-containing unreplicated DNA, whereas Topo IIα inhibition during mitosis impedes DNA decatenation at metaphase–anaphase transition, leading to the formation of UFB-containing DNA catenanes. Thus, Topo IIα activity is essential to prevent UFB formation in a cell-cycle-dependent manner and to promote DNA damage-free resolution of UFBs.
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Gemble, Simon; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Fontaine, Gaëlle; Lambert, Sarah; Amor-Guéret, Mounira (2020). Supplementary material from "Topoisomerase iiα prevents ultrafine anaphase bridges by two mechanisms". The Royal Society. Collection. https://doi.org/10.6084/m9.figshare.c.4969235.v1
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AUTHORS (6)
SG
Simon Gemble
GB
Géraldine Buhagiar-Labarchède
RO
Rosine Onclercq-Delic
GF
Gaëlle Fontaine
SL
Sarah Lambert
MA
Mounira Amor-Guéret