Altered cohesin dynamics and histone H3K9 modifications contribute to mitotic defects in thecbf11Δlipid metabolism mutant

Abstract

ABSTRACTMitotic fidelity is crucial for the faithful distribution of genetic information into the daughter cells. Many fungal species, including the fission yeastSchizosaccharomyces pombe, undergo a closed form of mitosis, during which the nuclear envelope does not break down. InS. pombenumerous processes have been identified that contribute to successful completion of mitosis. Notably, perturbations of lipid metabolism can lead to catastrophic mitosis and the “cut” phenotype. It was suggested that these mitotic defects are caused by insufficient membrane phospholipid supply during the anaphase nuclear expansion. However, it is not clear whether additional factors are involved. In this study we characterized in detail the mitosis in anS. pombemutant lacking the Cbf11 transcription factor, which regulates lipid metabolism genes. We show that incbf11Δcells mitotic defects appear already prior to anaphase, before the nuclear expansion begins. Moreover, we identify altered cohesin dynamics and centromeric chromatin structure as additional factors affecting mitotic fidelity in cells with disrupted lipid homeostasis, providing new insights into this fundamental biological process.