Ki67 regulates nuclear lipid accumulation at the chromosomal periphery to facilitate chromosome individualization during mitosis

Abstract

A hallmark of eukaryotic species is having distinct numbers of chromosomes surrounded by a nuclear envelope to separate nuclear transcription and RNA processing from cytosolic translation. In animal and plant cells undergoing open mitosis, the nuclear envelope disintegrates before the chromosomes divide into two daughter cells. To ensure faithful genome inheritance, chromosome individualization is involved in partitioning the fully condensed sister chromatids during mitosis. Ki67, a surfactant-like protein that forms a repulsive molecular brush around each pair of fully condensed sister chromatids during early mitosis, mediates chromosome individualization in vertebrates. Using a modified expansion microscopy methodology called TT-ExM for high-sensitivity and super-resolution imaging of proteins, lipids, and nuclear DNA, we found that intranuclear lipids in COS-7 cells not only are enriched at the chromosome periphery but are also excluded from the chromosome interior in a Ki67-dependent manner. Together with nuclear lipids, Ki67 forms the chromosomal envelope that mediates chromosome individualization. The transition from nuclear envelope to chromosomal envelope ensures continued separation of genetic material from cytoplasmic material during open mitosis.