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)
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
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
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomal duplications > aneuploidy
organism description > animal
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function
organism description > animal > mammal
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions
organism description > animal > mammal > rodent |
| CSHL Authors: |
|
| Communities: |
CSHL labs > Sheltzer lab
CSHL Cancer Center Program > Cancer Genetics and Genomics Program |
| Depositing User: |
Adrian Gomez
|
| Date: |
28 November 2019 |
| Date Deposited: |
18 Dec 2019 18:32 |
| Last Modified: |
02 Feb 2024 16:22 |
| PMCID: |
PMC6910827 |
| Related URLs: |
|
| Dataset ID: |
|
| URI: |
https://repository.cshl.edu/id/eprint/38787 |
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