NERemodelJaponicus · Deciphering the mechanisms underlying mitotic nuclear envelope remodelling in the fission yeast Schizosaccharomyces japonicus

Mitosis ensures faithful inheritance of genetic material in proliferating eukaryotic cells. Cellular genome is compartmentalized inside the nucleus, which is delimited by the double-membrane nuclear envelope (NE). The NE must be restructured during mitosis to allow chromosome segregation by the mitotic spindle and formation of the daughter nuclei. Eukaryotes perform this task using diverse approaches, ranging from fully “open” to fully “closed” mitosis depending on whether and when the NE breaks down. The fission yeast Schizosaccharomyces japonicus breaks the NE in anaphase, unlike its well-known relative S. pombe that undergoes closed mitosis. S. japonicus has already become an excellent discovery model providing critical insights into the rules underlying NE expansion and rearrangements of NE-chromatin contacts. Yet, we know little about the mitotic signalling and the effector mechanisms driving NE breakdown and reformation in this organism. Importantly, S. japonicus is uniquely suited for understanding mitotic nuclear membrane remodelling, as its mitosis does not involve the elaborate NE dynamics of higher eukaryotes, including disassembly and reassembly of nuclear pore complexes. I will combine cell biology, protein biochemistry, genetics, and next-generation sequencing approaches to understand: (1) how the evolutionarily conserved inner nuclear membrane protein Lem2 controls mitotic NE remodelling; (2) what are the molecular mechanisms of mitotic NE remodelling downstream of the important mitotic kinase Aurora B; and (3) what other novel factors drive NE breakdown and reformation in mitosis. Defects in NE remodelling result in spindle malfunction, aneuploidy and chromosome rearrangements that may compromise normal development and promote tumorigenesis. My work will provide a stripped-down view of membrane remodelling underlying NE breakdown and reformation in S. japonicus, with insights likely to be relevant to the open mitosis of metazoans, including humans.