TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution

Nature Communications
Ronan BroderickWojciech Niedzwiedz

Abstract

During mitosis, sister chromatids must be faithfully segregated to ensure that daughter cells receive one copy of each chromosome. However, following replication they often remain entangled. Topoisomerase IIα (TOP2A) has been proposed to resolve such entanglements, but the mechanisms governing TOP2A recruitment to these structures remain poorly understood. Here, we identify TOPBP1 as a novel interactor of TOP2A, and reveal that it is required for TOP2A recruitment to ultra-fine anaphase bridges (UFBs) in mitosis. The C-terminal region of TOPBP1 interacts with TOP2A, and TOPBP1 recruitment to UFBs requires its BRCT domain 5. Depletion of TOPBP1 leads to accumulation of UFBs, the majority of which arise from centromeric loci. Accordingly, expression of a TOPBP1 mutant that is defective in TOP2A binding phenocopies TOP2A depletion. These findings provide new mechanistic insights into how TOP2A promotes resolution of UFBs during mitosis, and highlights a pivotal role for TOPBP1 in this process.

References

Nov 4, 2000·Nature Genetics·S C TsaiE Seto
Dec 6, 2002·Nucleic Acids Research·Ciaran MorrisonWilliam C Earnshaw
Apr 26, 2005·Biochimica Et Biophysica Acta·Alicja CzubatyKrzysztof Staroń
May 18, 2005·DNA Repair·Valerie GarciaAntony M Carr
Mar 15, 2006·Cell·Akiko KumagaiWilliam G Dunphy
Jun 19, 2007·Genes & Development·Sinny DelacroixLarry M Karnitz
Jul 20, 2007·The Journal of Biological Chemistry·Joon LeeWilliam G Dunphy
Aug 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jun-Hyuk ChoiAziz Sancar
May 26, 2009·Nature Cell Biology·Kok Lung ChanIan D Hickson
Jun 6, 2009·Nucleic Acids Research·Mark JohnsonChristine J Farr
Oct 15, 2009·The Journal of Biological Chemistry·Kelly TownsendGrant S Stewart
Dec 2, 2009·HFSP Journal·Alessandro Vindigni, Ian D Hickson
Feb 11, 2010·Journal of Cell Science·Lily Hui-Ching WangErich A Nigg
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andrew N BlackfordAndrew S Turnell
Sep 28, 2010·The EMBO Journal·Rachele CescuttiThanos D Halazonetis
Feb 5, 2011·Experimental Cell Research·Sung Woong BangDeog Su Hwang
Apr 13, 2011·The Journal of Cell Biology·Jiadong WangJunjie Chen
May 28, 2011·The Biochemical Journal·Edward A Nam, David Cortez
Jul 26, 2011·Seminars in Cell & Developmental Biology·Kok Lung Chan, Ian D Hickson
Jan 27, 2012·Human Molecular Genetics·Andrew N BlackfordWojciech Niedzwiedz
Oct 16, 2012·Nucleic Acids Research·David L V BauerKalim U Mir
Feb 1, 2013·Current Pharmaceutical Design·Barbara PogorelčnikTom Solmajer
May 24, 2013·Nature·Emily C DykhuizenGerald R Crabtree
Jul 3, 2013·Nature Cell Biology·Songmin YingIan D Hickson
Jul 31, 2013·Structure·Charles Chung Yun LeungJ N Mark Glover
Jul 31, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jui LanChien-Feng Li
Aug 27, 2013·Molecular Cell·Andreas BiebricherIan D Hickson
Jan 1, 2014·The Journal of Cell Biology·Susanne M GermannMichael Lisby
May 6, 2014·Current Opinion in Genetics & Development·Ying LiuIan D Hickson

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Citations

Dec 25, 2015·Cell Cycle·Irene GallinaVibe H Oestergaard
Aug 13, 2015·Cell Cycle·Ronan Broderick, Wojciech Niedzwiedz
Jul 14, 2016·Nucleic Acids Research·Kevin Z L WuCorrado Santocanale
Aug 6, 2016·Frontiers in Genetics·Stefano Ferrari, Christian Gentili
Oct 18, 2016·Cell Cycle·Bingbing WanXiaolan Zhao
Oct 21, 2016·Nature Reviews. Molecular Cell Biology·Yves PommierJohn L Nitiss
Feb 7, 2017·Cell Cycle·Michalis Fragkos, Valeria Naim
Jul 23, 2015·PloS One·Christian GentiliStefano Ferrari
Dec 17, 2017·Scientific Reports·Beatriz Navarro-DomínguezMaría Dolores López-León
Nov 24, 2017·Cold Spring Harbor Symposia on Quantitative Biology·Kata SarlósIan D Hickson
Sep 27, 2018·Cell Cycle·Ying Wai Chan, Stephen C West
Dec 9, 2015·Nature Communications·Christian F NielsenIan D Hickson
Jun 14, 2020·Genes·Therese WilhelmValeria Naim
Aug 14, 2020·Genes·Alice FinardiRosella Visintin
Feb 14, 2019·The Journal of Cell Biology·Thomas E Bass, David Cortez
Dec 14, 2018·Genes·María Fernández-Casañas, Kok-Lung Chan
Jun 15, 2017·Cancer Research·Andrea EmanuelliMichael Blank
Jan 28, 2021·Molecular Cell·Camilla FrattiniAngelos Constantinou
Mar 30, 2021·EMBO Reports·Daniel BlakemorePaloma García
Sep 12, 2020·Seminars in Cell & Developmental Biology·Jonas BaggeMichael Lisby
Aug 30, 2021·DNA Repair·Mara De Marco Zompit, Manuel Stucki

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Methods Mentioned

BETA
two-hybrid
FACS
Assay
transfection
immunoprecipitation
proximity ligation

Software Mentioned

MASCOT
TOP2A
ImageJ
ZEN
FIJI
Huygens Professional ( Scientific Volume Imaging )

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