Abstract
Micronuclei are small nuclear cellular structures containing whole chromosomes or chromosomal fragments. While there is a lot of information available about the origin and formation of micronuclei, less is known about the fate of micronuclei and micronucleated cells. Possible fates include extrusion, degradation, reincorporation and persistence. Live cell imaging was performed to quantitatively analyse the fates of micronuclei and micronucleated cells occurring in vitro. Imaging was conducted for up to 96 h in HeLa-H2B-GFP cells treated with 0.5, 1 and 2 µg/ml etoposide. While a minority of micronuclei was reincorporated into the main nucleus during mitosis, the majority of micronuclei persisted without any alterations. Degradation and extrusion were observed rarely or never. The presence of micronuclei affected the proliferation of the daughter cells and also had an influence on cell death rates. Mitotic errors were found to be clearly increased in micronucleus-containing cells. The results show that micronuclei and micronucleated cells can, although delayed in cell cycle, sustain for multiple divisions.
Highlights
Micronuclei are small nuclear cellular structures usually formed during mitosis
When we observed micronucleus-containing cells in timelapse imaging, we found an increase in the number of micronuclei per cell at F0 and F1 in all treatment groups, which means that some cells contained more than one micronucleus, and a decrease over time in the following generations, meaning that some cells had lost or reintegrated the micronuclei or formed daughter cells without micronuclei (Fig. 1a)
The fate of micronuclei and micronucleated cells is a very important subject, because it addresses the question of the relevance of chromosomal mutations for the organism, which is essential for many biological processes including carcinogenesis
Summary
Micronuclei are small nuclear cellular structures usually formed during mitosis. They can contain whole chromosomes or chromosomal fragments, which can be distinguished by the presence of kinetochores in the micronuclei (Norppa and Falck 2003). Typical causes for the formation of micronuclei are, amongst others, spindle attachment. It is not clear if and to what extent DNA in micronuclei is replicated, transcribed or repaired (Hintzsche et al 2017). Crucial for correct function of these processes in micronuclei is the integrity of the micronuclear envelope. Envelope defects cause an impaired import and export of proteins into the micronucleus and have been shown to reduce DNA damage repair, which in turn could lead to chromothripsis (Terradas et al 2016). One mechanistic explanation for this might be incorrect lamin B1 assembly
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