Topoisomerase IIα prevents ultrafine anaphase bridges by two mechanisms

Author:

Gemble Simon123ORCID,Buhagiar-Labarchède Géraldine123ORCID,Onclercq-Delic Rosine123ORCID,Fontaine Gaëlle123ORCID,Lambert Sarah123ORCID,Amor-Guéret Mounira123ORCID

Affiliation:

1. Institut Curie, PSL Research University, UMR 3348, Centre de Recherche, Orsay, France

2. CNRS UMR 3348, Centre Universitaire, Bât. 110. 91405, Orsay, France

3. Université Paris Saclay, UMR 3348, Centre Universitaire d'Orsay, France

Abstract

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.

Funder

Association pour la Recherche sur le Cancer

Ministère de l'Education, de l'Enseignement Supérieur et de la Recherche

Agence Nationale de la Recherche

Centre National de la Recherche Scientifique

Institut Curie

Ligue Contre le Cancer

Publisher

The Royal Society

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology,General Neuroscience

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3