TY  - JOUR
A1  - Kneissig, Maja
A1  - Keuper, Kristina
A1  - de Pagter, Mirjam S
A1  - Roosmalen, Markus J van
A1  - Martin, Jana
A1  - Otto, Hannah
A1  - Passerini, Verena
A1  - Campos Sparr, Aline
A1  - Renkens, Ivo
A1  - Kropveld, Fenna
A1  - Vasudevan, Anand
A1  - Sheltzer, Jason M
A1  - Kloosterman, Wigard P
A1  - Storchova, Zuzana
T1  - Micronuclei-based model system reveals functional consequences of chromothripsis in human cells
T2  - eLife
N2  - 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.
Y1  - 2019
UR  - https://kluedo.ub.uni-kl.de/frontdoor/index/index/docId/5899
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:386-kluedo-58994
SN  - 2050-084X
IS  - 2019;8:e50292
PB  - eLife Sciences Publications
ER  -