Fig. 3. MRE11 promotes senescence in BJ-RAS^V12 fibroblasts.

a Effect of MRE11 inhibition on BJ-RAS^V12 cell growth. Untreated (Ctrl) or RAS-induced (Dox, 10 μg/ml) BJ-RAS^V12 cells were grown in the presence (+Mirin) or the absence (DMSO) of 10 µM Mirin. Cumulative cell number was calculated by counting cells during five consecutive passages, with each passage lasting 3–4 days in culture. A representative experiment is shown (n = 2). b Representative images of SA-β-gal staining in BJ-RAS^V12 fibroblasts overexpressing RAS^V12 and treated or not with 10 µM Mirin for 8 and 14 days (n = 3). Scale bars are 100 μm. c MRE11 inhibition prevents the induction of senescence-associated β-galactosidase (SA-β-gal). BJ-RAS^V12 fibroblasts were induced with 10 μg/ml doxycycline (Dox) for 8 and 14 days in the presence or absence of 10 μM Mirin. Cells were stained for SA-β-gal activity and the frequency of SA-β-gal positive cells was scored. Mean, SD and p values (two-sided unpaired t-test) are shown for three independent experiments. d Effect of MRE11 inhibitors on cell proliferation. BJ-RAS^V12 fibroblasts were induced or not with 10 μg/ml doxycycline (Dox). The frequency of BrdU-positive cells, at least 74 cells were scored per condition in each independent experiment, before and after RAS^V12 induction was monitored in the presence or the absence of 10 μM Mirin, 10 μM PFM01 and 10 μM PFM39 after 8 days of treatment. Non-treated (-) and DMSO-treated cells were used as controls. Mean, SD, and p values (two-sided unpaired t-test) are shown. Each point represents a biological replicate. Source data are provided as a Source Data file.