The Mre11–Rad50–Nbs1 complex mediates the robust recruitment of Polo to DNA lesions during mitosis in Drosophila
Cédric Landmann1,a, Prisciliia Pierre-Eliès1,a, Damien Goutte-Gattat1, Émilie Montembault1, Marie-Charlotte Claverie1, and Anne Royou1,b
1CNRS, UMR5095, University of Bordeaux, European Institute of Chemistry and Biology, 2 rue Robert Escarpit, 33607 Pessac, France
aThese authors contributed equally to this work.
bCorresponding author: a.royou@iecb.u-bordeaux.fr
This article was published in the Journal of Cell Science under the “Green Open Access” model. As one of the authors, I make it available here as allowed by the journal’s policy on self-archiving.
Right to re-use for teaching purpose is granted on the condition that it is non-commercial; for any other type of re-use, permission must be sought from the editor.
J. Cell Sci.,133(13):jcs244442. doi:10.1242/jcs.244442 [full text]
Abstract
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. There two proteins display distinct kinetics. Whereas Polo kinetics as 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.
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