The Mre11-Rad50-Nbs1 complex mediates the robust recruitment of Polo to DNA lesions during mitosis in Drosophila

Autor: Landmann, Cedric, Pierre-Elies, Priscillia, Goutte-Gattat, Damien, Montembault, Emilie, Claverie, Marie-Charlotte, Royou, Anne
Přispěvatelé: Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Montembault, Emilie
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Cell Science
Journal of Cell Science, Company of Biologists, 2020, 133 (13), pp.jcs244442. ⟨10.1242/jcs.244442⟩
Journal of Cell Science, 2020, 133 (13), pp.jcs244442. ⟨10.1242/jcs.244442⟩
ISSN: 0021-9533
1477-9137
DOI: 10.1242/jcs.244442⟩
Popis: International audience; 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 micro-irradiation of single chromosomes, we analyze the dynamics of Polo and Mre11 at DNA lesions during mitosis in Drosophila. These two proteins display distinct kinetics. Whereas Polo kinetics at double-strand breaks (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 was sufficient to recruit Polo. Our study highlights a novel pathway that links the DSB sensor Mre11-Rad50-Nbs1 complex and Polo kinase to initiate a prompt, decisive response to the presence of DNA damage during mitosis.
Databáze: OpenAIRE