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Two physiological responses to protect tissues from nuclear defects
Published on November 20, 2024
A new study by the Cell Cycle Regulation Research Unit, headed by Vincent Archambault, identifies two physiological responses activated when nuclear reformation defects are detected by the cells at the end of their division. These responses play a crucial role in protecting tissue integrity during development. Published in the journal PLOS Biology, the project was led by doctoral student Jingjing Li.
An essential mechanism for reforming nuclei after cell division
When eukaryotic cells divide, their nuclei undergo major transformations: the nuclear envelope breaks down, allowing chromosomes to be evenly distributed between the two daughter cells, then reforms to form two new nuclei. The reformation of the nuclear envelope is a multi- step process, involving several proteins. If it fails, in whole or in part, the nuclei can suffer major structural defects that affect the state of the cell.
Through experiments in Drosophila fruit flies and in cultured Drosophila cells, the Archambault team has succeeded in characterizing a mechanism by which the Ankle2 protein promotes nuclear envelope reformation. The results also reveal that failure of this mechanism leads to serious nuclear defects at the end of cell division.
Cells born with nuclear defects can undergo at least two distinct cellular fates
The team then took advantage of the identified perturbations to study the cellular and physiological consequences of nuclear reformation defects during fly development. Their observations suggest that cells with defective nuclei can take at least two different routes. In some cases, the p53 protein activates a checkpoint that suspends the cell cycle and allows repair of nuclear damage. In other cases, apoptosis, the process of cell death, functions as a quality-control mechanism that eliminates defective cells and promotes normal tissue development.
Prior to the Archambault study, very little was known about the physiological responses of organisms to defects in nuclear reformation, which are common in cancer. Since the molecular mechanisms controlling cell division and survival are very similar between animal species, the findings of this study could be validated in humans.
Cited study
Li J, Jordana L, Mehsen H, Wang X, Archambault V (2024) Nuclear reassembly defects after mitosis trigger apoptotic and p53-dependent safeguard mechanisms in Drosophila. PLoS Biol 22(8): e3002780. https://doi.org/10.1371/journal.pbio.3002780
