The Mre11-Rad50-Nbs1 complex mediates the robust recruitment of Polo to DNA lesions during mitosis
| Autor: | Marie-Charlotte Claverie, Damien Goutte-Gattat, Emilie Montembault, Anne Royou, Priscillia Pierre-Elies, Cedric Landmann |
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| Rok vydání: | 2020 |
| Předmět: |
DNA Repair
DNA damage Mitosis Cell Cycle Proteins CDC20 Protein Serine-Threonine Kinases Biology 03 medical and health sciences 0302 clinical medicine Animals Drosophila Proteins 030304 developmental biology Anaphase MRE11 Homologue Protein 0303 health sciences Endodeoxyribonucleases fungi Polo kinase DNA Cell Biology Acid Anhydride Hydrolases Cell biology Chromatin DNA-Binding Proteins enzymes and coenzymes (carbohydrates) Exodeoxyribonucleases MRN complex 030220 oncology & carcinogenesis Rad50 Drosophila biological phenomena cell phenomena and immunity |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | The DNA damage sensor, Mre11-Rad50-Nbs1 complex, and Polo kinase are recruited to DNA lesions during mitosis. However, their mechanism of recruitment is elusive. Here, using live-cell imaging combined with the micro-irradiation of single chromosomes, we analyze the dynamics of Polo and Mre11 at DNA lesions during mitosis. The two proteins display distinct kinetics. While Polo kinetics at DSBs are Cdk1-driven, Mre11 promptly but briefly associates with DSBs regardless of the phase of mitosis and re-associates with DSBs in the proceeding interphase. Mechanistically, Polo kinase activity is required for its own recruitment and that of the mitotic proteins BubR1 and Bub3 to DSBs. Moreover, depletion of Rad50 severely impaired Polo kinetics at mitotic DSBs. Conversely, ectopic tethering of Mre11 to chromatin is sufficient to recruit Polo. Our study highlights a novel pathway that links the DSB sensor MRN complex and Polo kinase to initiate a prompt, decisive response to the presence of DNA damage during mitosis. |
| Databáze: | OpenAIRE |
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