Extended Data Fig. 9: NUMEN enables in situ NHEJ repair of heterochromatic breaks and maintaining of genome stability.

a, MDA-MB-231 cells were treated with DMSO, zeocin (100 μg ml⁻¹ for 4 h), bleomycin (40 μg ml⁻¹ for 4 h), IR (2 Gy and harvested 2 h later) or cisplatin (2.5 μM for 4 h) before immunofluorescence analysis using antibodies to γH2AX (green) and H3K9me2 (red). DAPI was used to stain the nuclei (blue). Scale bars, 5 μm. b, Analysis of CNV counts from four cancer types with significant negative correlations from a. LIHC (n = 337), COAD (n = 407), HNSC (n = 468), and BRCA (n = 1,027) samples with valid outcome data were grouped by the expression levels of BRCA1 and NUMEN (median cutoff) and are shown in violin plots. Each box outline shows the 25th and 75th percentiles, and the solid line indicates the median value. Whiskers extend to the most extreme data points that are no more than 1.5× the interquartile range. n, number of subgroup samples. Statistical analysis was performed using a two-tailed Mann–Whitney U-test. c, DSB repair pathway choice is tightly regulated to ensure the faithful repair of chromosome breaks. Nuclear compartmentation may help shape such decisions. We propose that nuclear membrane anchoring of NUMEN facilitates the establishment of an environment that favours NHEJ for the repair of repetitive DNA sequences at LADs as well as lesions dynamically moving from the nuclear interior to the periphery. NUMEN may thus antagonize HDR near the nuclear periphery and help minimize ectopic repair between heterochromatic repetitive sequences. Source numerical data are provided.