New pathways regulating MBF-dependent transcription in fission yeast
At the end of G1 phase, cells have to decide between continue proliferation or remain in a quiescent state (G0). This decision point, known as “Start” in yeast and “Restriction Point” in metazoans, marks irreversibly the commitment to the completion of a new cell cycle, and is regulated mainly by th...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/672476 |
| Acceso en línea: | http://hdl.handle.net/10803/672476 |
| Access Level: | acceso abierto |
| Palabra clave: | MBF Schizosaccaromyces pombe Cicle cel.lular G1/S transition Transcripció N-end rule pathway TORC Nutritional depletion Glucosa Short-lived reporter 576 |
| Sumario: | At the end of G1 phase, cells have to decide between continue proliferation or remain in a quiescent state (G0). This decision point, known as “Start” in yeast and “Restriction Point” in metazoans, marks irreversibly the commitment to the completion of a new cell cycle, and is regulated mainly by the activity of the G1 CDK and the induction of the G1-to-S transcriptional program. The MBF transcription factor complex (functional homolog of pRB-E2F in metazoans) drives the G1-to-S transcriptional wave in the fission yeast Schizosaccharomyces pombe. We have previously described how the co-repressors Nrm1 and Yox1 bind to MBF complex at the end of S phase, inhibiting the MBF activity. However, the mechanisms involved in the activation of MBF at the onset of an unperturbed cell cycle have remained elusive. Here, we show that Nrm1 is the responsible for the activation of the MBF-dependent transcription through a two-step mechanism. Its phosphorylation by CDK1 and its posterior degradation by APCSte9 induce the irreversible MBF activation until the end of S phase. We have also studied the role of chromatin remodelers in the control of the G1-to-S transcriptional program. In this sense, we have found that chromatin-remodeling complexes SWI/SNF and RSC are recruited to MBF-regulated genes, having a clear impact in the activation of the G1-to-S transcriptional wave. Furthermore, we have created a short-lived fluorescent reporter to measure small and transient changes in the MBF activity in vivo by flow cytometry, to further identify new MBF regulators. |
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