Micronuclei-based model system reveals functional consequences of chromothripsis in human cells
| Autor: | Markus J. van Roosmalen, Fenna Kropveld, Anand Vasudevan, Zuzana Storchova, Jana Martin, Wigard P. Kloosterman, Ivo Renkens, Jason M. Sheltzer, Aline Campos Sparr, Hannah Otto, Maja Kneissig, Verena Passerini, Kristina Keuper, Mirjam S. de Pagter |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Aneuploidy Germline Mice 0302 clinical medicine cell biology rearrangements genetics chromosome Biology (General) Chromothripsis Lamin Type B General Neuroscience General Medicine Cell biology 030220 oncology & carcinogenesis Medicine Research Article Human DNA Replication QH301-705.5 Chromosome Transfer Science Biology General Biochemistry Genetics and Molecular Biology Genomic Instability Cell Line 03 medical and health sciences ddc:570 medicine genomics Animals Humans human aneuploidy Micronuclei Chromosome-Defective Cell Nucleus General Immunology and Microbiology DNA replication Chromosome Genetics and Genomics Cell Biology medicine.disease 030104 developmental biology micronuclei Cancer cell chromothripsis Lamin DNA Damage |
| Zdroj: | eLife, Vol 8 (2019) eLife ELIFE eLife, 8. eLife Sciences Publications |
| ISSN: | 2050-084X |
| Popis: | © 2019, Kneissig et al. 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. |
| Databáze: | OpenAIRE |
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