Topoisomerase IIα prevents ultrafine anaphase bridges by two mechanisms
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- Simon Gemble
- Institut Curie, PSL Research University, UMR 3348, Centre de Recherche, Orsay, France
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- Géraldine Buhagiar-Labarchède
- Institut Curie, PSL Research University, UMR 3348, Centre de Recherche, Orsay, France
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- Rosine Onclercq-Delic
- Institut Curie, PSL Research University, UMR 3348, Centre de Recherche, Orsay, France
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- Gaëlle Fontaine
- Institut Curie, PSL Research University, UMR 3348, Centre de Recherche, Orsay, France
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- Sarah Lambert
- Institut Curie, PSL Research University, UMR 3348, Centre de Recherche, Orsay, France
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- Mounira Amor-Guéret
- Institut Curie, PSL Research University, UMR 3348, Centre de Recherche, Orsay, France
説明
<jats:p>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.</jats:p>
収録刊行物
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- Open Biology
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Open Biology 10 (5), 190259-, 2020-05
The Royal Society
