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

Kneissig, M., Keuper, K., de Pagter, M. S., van Roosmalen, M. J., Martin, J., Otto, H., Passerini, V., Campos Sparr, A., Renkens, I., Kropveld, F., Vasudevan, A., Sheltzer, J. M., Kloosterman, W. P., Storchova, Z. (November 2019) Micronuclei-based model system reveals functional consequences of chromothripsis in human cells. Elife, 8. e50292. ISSN 2050-084x (Public Dataset)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/31778112
DOI: 10.7554/eLife.50292

Abstract

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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomal duplications > aneuploidy
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function
CSHL Authors:
Communities: CSHL labs > Sheltzer lab
Depositing User: Adrian Gomez
Date: 28 November 2019
Date Deposited: 18 Dec 2019 18:32
Last Modified: 15 Jan 2020 14:52
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URI: https://repository.cshl.edu/id/eprint/38787

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