Cellular response upon proliferation in the presence of an active mitotic checkpoint
| Autor: | Stefano Maffini, Elena Chiroli, Andrea Ciliberto, Vittoria Matafora, Angela Bachi, Fridolin Gross, Claudio Vernieri, Andrea Corno, Marco Cosentino Lagomarsino |
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| Rok vydání: | 2019 |
| Předmět: |
Cell cycle checkpoint
Cell division Health Toxicology and Mutagenesis Mitosis Cell Cycle Proteins Plant Science Biology Models Biological Biochemistry Genetics and Molecular Biology (miscellaneous) 03 medical and health sciences 0302 clinical medicine Single-cell analysis Research Articles Cell Proliferation Cell Size 030304 developmental biology 0303 health sciences Ecology Cell growth Gene Expression Profiling Translation (biology) Cell Cycle Checkpoints Cell cycle Cell biology Spindle checkpoint Mutation Single-Cell Analysis Transcriptome Cell Division 030217 neurology & neurosurgery Research Article |
| Zdroj: | Life Science Alliance |
| ISSN: | 2575-1077 |
| Popis: | Cells that replicate with an active mitotic checkpoint remain capable to mount multiple times an efficient arrest, are bigger than unperturbed cells, rely more heavily on Cdh1, and have an altered protein expression profile. Eukaryotic cells treated with microtubule-targeting agents activate the spindle assembly checkpoint to arrest in mitosis and prevent chromosome mis-segregation. A fraction of mitotically arrested cells overcomes the block and proliferates even under persistent checkpoint-activating conditions. Here, we asked what allows proliferation in such unfavourable conditions. We report that yeast cells are delayed in mitosis at each division, implying that their spindle assembly checkpoint remains responsive. The arrest causes their cell cycle to be elongated and results in a size increase. Growth saturates at mitosis and correlates with the repression of various factors involved in translation. Contrary to unperturbed cells, growth of cells with an active checkpoint requires Cdh1. This peculiar cell cycle correlates with global changes in protein expression whose signatures partly overlap with the environmental stress response. Hence, cells dividing with an active checkpoint develop recognisable specific traits that allow them to successfully complete cell division notwithstanding a constant mitotic checkpoint arrest. These properties distinguish them from unperturbed cells. Our observation may have implications for the identification of new therapeutic windows and targets in tumors. |
| Databáze: | OpenAIRE |
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