Chromosome organisation during cell division and effects on nuclear shape in interphase

Abnormally shaped, lobed nuclei are often observed in cancer cells, although the mechanisms causing these misshapen nuclei are unknown. Here, the effects of chromosome organization during cell division on nuclear shape were measured as solidity (roundness). One consequence of abnormal nuclear shape is that misshapen cell nuclei may alter gene expression, dramatically shifting normal cell activity and contributing to disease. Many proteins, including the class of molecular motors, called kinesins, direct regular cell activities including cell division. The kinesin Kif18A is responsible for maintaining chromosome alignment in the middle of a dividing cell before chromosomes segregate, producing two daughter cells. Without Kif18A, chromosomes are unaligned at metaphase, causing disordered chromosome segregation. In this study, it was investigated whether proper chromosome alignment during cell division impacts the resulting nuclear shape of daughter cells. Live cells transfected with a fluorescently labeled plasmid (GFP-H2B, to label chromatin) were imaged and analyzed using the program ImageJ to observe chromosome dynamics and cell shape after division. In the absence of Kif18A, daughter cell nuclei had lower solidity measurements, meaning nuclei were more abnormally shaped (p<0.0001). Furthermore, in the absence of Kif18A, cells were more likely to have lagging chromosomes which led to the production of micronuclei (whole or fragmented chromosomes separated from the main nucleus). Additionally, population-wide, Kif18A mutants had more cells with abnormally shaped nuclei compared to the control. These results suggest that chromosome alignment during cell division impacts nuclear shape of daughter cells, and is a possible mechanism leading to abnormal nuclear shape.