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Micronuclei-based model system reveals functional consequences of chromothripsis in human cells

  • Cancer cells often harbor chromosomes in abnormal numbers and with aberrant structure. The consequences of these chromosomal aberrations are difficult to study in cancer, and therefore several model systems have been developed in recent years. We show that human cells with extra chromosome engineered via microcell-mediated chromosome transfer often gain massive chromosomal rearrangements. The rearrangements arose by chromosome shattering and rejoining as well as by replication-dependent mechanisms. We show that the isolated micronuclei lack functional lamin B1 and become prone to envelope rupture, which leads to DNA damage and aberrant replication. The presence of functional lamin B1 partly correlates with micronuclei size, suggesting that the proper assembly of nuclear envelope might be sensitive to membrane curvature. The chromosomal rearrangements in trisomic cells provide growth advantage compared to cells without rearrangements. Our model system enables to study mechanisms of massive chromosomal rearrangements of any chromosome and their consequences in human cells.
Author:Maja KneissigORCiD, Kristina KeuperORCiD, Mirjam S de Pagter, Markus J van Roosmalen, Jana Martin, Hannah Otto, Verena Passerini, Aline Campos Sparr, Ivo Renkens, Fenna Kropveld, Anand Vasudevan, Jason M Sheltzer, Wigard P Kloosterman, Zuzana StorchovaORCiD
URN (permanent link):urn:nbn:de:hbz:386-kluedo-58994
Parent Title (English):eLife
Publisher:eLife Sciences Publications
Document Type:Article
Language of publication:English
Publication Date:2019/11/28
Year of Publication:2019
Publishing Institute:Technische Universität Kaiserslautern
Date of the Publication (Server):2020/02/18
Number of page:20
Faculties / Organisational entities:Fachbereich Biologie
DDC-Cassification:5 Naturwissenschaften und Mathematik / 570 Biowissenschaften, Biologie
Licence (German):Zweitveröffentlichung