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

Cédric Landmann, Priscillia Pierre-Eliès, Damien Goutte-Gattat, Émilie Montembault, Marie-Charlotte Claverie, and Anne Royou.

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 dymamics of Polo and Mre11 at DNA lesions during mitosis. The two proteins display distinct kinetics. While Polo kinetics at DSBs are Cdk1-drivem, 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 damages during mitosis.

View online: J. Cell Sci., 133(13):jcs244442