Nuclear stiffness through lamin A/C overexpression differentially modulates chromosomal instability biomarkers

Here, we examined whether increasing nuclear envelope stiffness through lamin A/C overexpression could affect the formation of toroidal nuclei and micronuclei. Interestingly, lamin A/C overexpression led to an increase in toroidal nuclei while reducing micronuclei prevalence. We demonstrated that chromatin compaction and nuclear stiffness drive the formation of toroidal nuclei. Furthermore, inhibition of autophagy and lysosomal function elevated the frequency of toroidal nuclei without affecting the number of micronuclei in the whole cell population. We demonstrated that this divergence between the two CIN biomarkers is independent of defects in lamin A processing. Conclusions and significance: These findings uncover a complex interplay between nuclear architecture and levels of CIN, advancing our understanding of the mechanisms supporting genomic stability and further contributing to cancer biology.

These findings uncover a complex interplay between nuclear architecture and levels of CIN, advancing our understanding of the mechanisms supporting genomic stability and further contributing to cancer biology.