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

Maja Kneissig, Kristina Keuper, Mirjam S. De Pagter, Markus J. Van Roosmalen, Jana Martin, Hannah Otto, Verena Passerini, Aline Campos Sparr, Ivo Renkens, Fenna Kropveld, Anand Vasudevan, Jason Sheltzer, Wigard P. Kloosterman, Zuzana Storchová

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

61 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Artikelnummere50292
TijdschrifteLife
Volume8
DOI's
StatusGepubliceerd - nov. 2019
Extern gepubliceerdJa

Vingerafdruk

Duik in de onderzoeksthema's van 'Micronuclei-based model system reveals functional consequences of chromothripsis in human cells'. Samen vormen ze een unieke vingerafdruk.

Citeer dit