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

Autor:	Landmann C; CNRS, UMR5095, University of Bordeaux, European Institute of Chemistry and Biology, 2 rue Robert Escarpit, 33607 Pessac, France., Pierre-Elies P; CNRS, UMR5095, University of Bordeaux, European Institute of Chemistry and Biology, 2 rue Robert Escarpit, 33607 Pessac, France., Goutte-Gattat D; CNRS, UMR5095, University of Bordeaux, European Institute of Chemistry and Biology, 2 rue Robert Escarpit, 33607 Pessac, France., Montembault E; CNRS, UMR5095, University of Bordeaux, European Institute of Chemistry and Biology, 2 rue Robert Escarpit, 33607 Pessac, France., Claverie MC; CNRS, UMR5095, University of Bordeaux, European Institute of Chemistry and Biology, 2 rue Robert Escarpit, 33607 Pessac, France., Royou A; CNRS, UMR5095, University of Bordeaux, European Institute of Chemistry and Biology, 2 rue Robert Escarpit, 33607 Pessac, France a.royou@iecb.u-bordeaux.fr.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2020 Jul 01; Vol. 133 (13). Date of Electronic Publication: 2020 Jul 01.
DOI:	10.1242/jcs.244442
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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