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Ndd1 Turnover by SCF Is Inhibited by the DNA Damage Checkpoint in


All cells must regulate cell division in response to extracellular and intracellular cues, and one of the most critical steps to regulate is the process of cell division, or mitosis. In response to DNA damage in budding yeast, cells activate a checkpoint that promotes DNA repair and arrests the cell cycle before division to give the cell time to repair the lesion. One of the key regulators of mitosis is an essential transcription factor called Ndd1. Ndd1 is known to be regulated by transcription and phosphorylation, both in unperturbed cells and following exposure to DNA damage. Here, we show that Ndd1 protein turnover is also regulated in both situations. Ndd1 is degraded quickly during an unperturbed cell cycle, but is strongly stabilized following exposure to DNA damage. We identify the machinery that targets Ndd1 for turnover and the signaling pathways required to stabilize Ndd1 in response to DNA damage. Maintaining high levels of Ndd1 after exposure to DNA damage may allow the cell to reactivate Ndd1 after the damage has been repaired to promote mitosis.


Vyšlo v časopise: Ndd1 Turnover by SCF Is Inhibited by the DNA Damage Checkpoint in. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005162
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005162

Souhrn

All cells must regulate cell division in response to extracellular and intracellular cues, and one of the most critical steps to regulate is the process of cell division, or mitosis. In response to DNA damage in budding yeast, cells activate a checkpoint that promotes DNA repair and arrests the cell cycle before division to give the cell time to repair the lesion. One of the key regulators of mitosis is an essential transcription factor called Ndd1. Ndd1 is known to be regulated by transcription and phosphorylation, both in unperturbed cells and following exposure to DNA damage. Here, we show that Ndd1 protein turnover is also regulated in both situations. Ndd1 is degraded quickly during an unperturbed cell cycle, but is strongly stabilized following exposure to DNA damage. We identify the machinery that targets Ndd1 for turnover and the signaling pathways required to stabilize Ndd1 in response to DNA damage. Maintaining high levels of Ndd1 after exposure to DNA damage may allow the cell to reactivate Ndd1 after the damage has been repaired to promote mitosis.


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