Fig. 4: Loss of MMS22L impairs HRR function in PCa cells.

a Immunoblot analysis of cleaved PARP and γ-H2AX in AAVS1 control and MMS22L-KO C4-2B cells after olaparib treatment for 72 h. The experiment was repeated independently three times with similar results. b Representative images of two biologically independent experiments and quantification of γ-H2AX foci in AAVS1 control and MMS22L-KO C4-2B cells after olaparib treatment for 24 h. More than 100 cells were analyzed per condition. Solid lines inside the violin indicate the median. Scale bar = 5 μm. c Cell cycle analysis (upper panel) of AAVS1 control, MMS22L-KO and TONSL-KO LNCaP, and C4-2B cells after treatment with DMSO or olaparib for 72 h. The percentage of cells (lower panel) in each phase of the cell cycle is shown. The experiment was repeated independently twice with similar results. d Representative images and quantification of RAD51 foci in AAVS1 control and MMS22L-KO C4-2B cells stably infected with TET-inducible MMS22L gene after olaparib treatment in the presence or absence of doxycycline (0.15 μg/ml) for 24 h. Dots indicate each replicate with more than 100 cells analyzed. Data are presented as mean ± SD of three biologically independent replicates. Scale bar = 5 μm. e Ranked HRD scores (Upper panel) in PCa tumors with BRCA and/or MMS22L genomic alterations as indicated. Comparison of HRD scores (lower panel) between five patient groups classified based on BRCA and MMS22L status (n = 196, 48, 11, 3, and 9 tumor samples in each group, respectively). Data are presented as boxplot indicating median, 25th-75th percentile (box), and minimum and maximum values (whiskers). f The mRNA level of MMS22L in PCa tumors with Intact MMS22L, heterozygous (Hetero) deletion, and homozygous (Homo) deletion of MMS22L in the TCGA cohort and the SU2C/PCF cohort (n = 487 and 196 tumor samples, respectively)^25,26. g Kaplan–Meier survival curves in the Long PCa cohort¹¹¹ (n = 50 versus 50 tumor samples) and the Cambridge PCa cohort¹¹² (n = 63 versus 62 tumor samples) based on the MMS22L mRNA expression level (lower versus higher). A log-rank test was carried out to examine the survival difference. In (b) and (d–f) the p-values were determined using two-sided t-test. ns = not significant. Source data are provided as a Source Data file.