Protective role of RAD50 on chromatin bridges during abnormal cytokinesis

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Bianca Schröder-HeurichThilo Dörk

Abstract

Faithful chromosome segregation is required for preserving genomic integrity. Failure of this process may entail chromatin bridges preventing normal cytokinesis. To test whether RAD50, a protein normally involved in DNA double-strand break repair, is involved in abnormal cytokinesis and formation of chromatin bridges, we used immunocytochemical and protein interaction assays. RAD50 localizes to chromatin bridges during aberrant cytokinesis and subsequent stages of the cell cycle, either decorating the entire bridge or focally accumulating at the midbody zone. Ionizing radiation led to an ∼4-fold increase in the rate of chromatin bridges in an ataxia telangiectatica mutated (ATM)-dependent manner in human RAD50-proficient fibroblasts but not in RAD50-deficient cells. Cells with a RAD50-positive chromatin bridge were able to continue cell cycling and to progress through S phase (44%), whereas RAD50 knockdown caused a deficiency in chromatin bridges as well as an ∼4-fold prolonged duration of mitosis. RAD50 colocalized and directly interacted with Aurora B kinase and phospho-histone H3, and Aurora B kinase inhibition led to a deficiency in RAD50-positive bridges. Based on these observations, we propose that RAD50 is a crucial fact...Continue Reading

References

Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·G LuoJ H Petrini
Jul 27, 2001·The Journal of Biological Chemistry·D E AndersonH P Erickson
Oct 13, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A Losada, T Hirano
Oct 25, 2001·Proceedings of the National Academy of Sciences of the United States of America·D GisselssonN Mandahl
Feb 28, 2002·Genome Biology·Susan H HarveyMatthew J O'Connell
May 25, 2004·Chromosoma·Diane R HoffelderWilliam S Saunders
Sep 18, 2004·Science·Matthew J DanielsAshok R Venkitaraman
Apr 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ylva StewéniusDavid Gisselsson
May 5, 2005·Nature Structural & Molecular Biology·Michael Lichten
Apr 25, 2006·Nature Reviews. Molecular Cell Biology·Tatsuya Hirano
Mar 17, 2007·Genes, Chromosomes & Cancer·Ceyda AcilanWilliam S Saunders
Jan 20, 2009·Nucleic Acids Research·Eddy van der LindenClaire Wyman
Feb 11, 2009·Cell·Chun-Ting Chen, Stephen Doxsey
Feb 11, 2009·Cell·Patrick SteigemannDaniel W Gerlich
Mar 25, 2009·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Eri KinoshitaClaire Wyman
May 5, 2009·American Journal of Human Genetics·Regina WaltesThilo Dörk
May 16, 2009·Biochemical Society Transactions·Aaron A GoodarziPenny A Jeggo
Oct 6, 2010·The Journal of Clinical Investigation·Patrizia VinciguerraAlan D D'Andrea
Jan 22, 2011·Nature Reviews. Molecular Cell Biology·Travis H Stracker, John H J Petrini
Jul 16, 2011·The Journal of Biological Chemistry·Magtouf GateiMartin F Lavin
Aug 14, 2012·Molecular Cell·Mireille Tittel-ElmerJennifer A Cobb
Feb 26, 2013·Molecular Cell·Lorene RozierYinghui Mao

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Citations

Dec 20, 2017·Frontiers in Immunology·Barbara PietruchaThilo Dörk
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lea VölkeningThilo Dörk
Mar 27, 2020·American Journal of Medical Genetics. Part a·Aviël RagaminGrazia M S Mancini
Sep 19, 2015·Cell Death and Differentiation·P GrigaraviciusP-O Frappart

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