Fig 2: RAD51C c.571 + 4A > G segregates with breast and/or ovarian cancer in five multiplex families (a–d) that tested negative for variants in BRCA1, BRCA2, and other high and moderate cancer susceptibility genes. Family pedigree number, age at cancer diagnosis and current age of individuals are indicated. Black shade: diagnosis of breast and/or ovarian cancer; gray shade: diagnosis with cancer unrelated to HBOC; white shade: no cancer diagnosis; arrows: probands; slash: deceased; +: RAD51C c.571 + 4A > G heterozygote; -: RAD51C c.571 + 4 wild-type

Fig 3: Working model of TAZ regulating telomere length in TNBC cells. In TAZ-knocked down TNBC cells, the binding of TAZ-TEADs to the promoter of Rad51C was decreased, and the transcription of Rad51C was further impaired. Lack of Rad51C causes the telomere shortening and impaired telomere functions. The protein levels of shelterin components is decreased, along with increased telomere-induced DNA damage foci (TIF) and DDR activation. Moreover, the increased levels of TERRAs in TAZ-deficient cells may also contribute to the observed telomere loss phenotype

Fig 4: Rad51C is a direct YAP/TAZ-TEAD target gene. A TEAD4 binding signals in the promoter of Rad51C from ENCODE ChIP-seq database (https://www.encodeproject.org) were analyzed from A549 (lung cancer), H1 (human embryonic stem cells), HCT-116 (colon cancer), MCF-7 (breast cancer), and SK-N-SH (neuroblastoma) cells. B Western blot analysis of TAZ and TEAD4 protein levels in BT549 cells as indicated. Quantification of Western blots is shown in Additional file 1: Fig. S5N. C ChIP analyses in the indicated BT549 cells were performed to determine the enrichment of TRAD4 on the Rad51C promoter region. IgG was used as a negative control. D Luciferase reporter assays were performed to test the activities of Rad51C promoter fragments in the indicated BT549. Data are presented as mean ± SEM. At least three repeats were carried out for each test. The p values were determined by Student's t-test. NS, not significant, *p < 0.05, **p < 0.01, ***p < 0.001

Fig 5: Knockdown of TAZ inhibits Rad51C transcription, and TAZ maintains telomere length through Rad51C. A Western blot analysis of TAZ and Rad51C protein levels in MDA-MB-231 and BT549 cells as indicated. Quantification of Western blots is shown in Additional file 1: Fig. S5J. B qPCR analyses to determine the mRNA levels of Rad51C in MDA-MB-231 and BT549 cells as indicated. C Western blot analysis in BT549 cells treated as indicated to examine the protein levels of Rad51C. Quantification of Western blots is shown in Additional file 1: Fig. S5K. D Telomere-specific qPCR analysis to determine the relative telomere length in the indicated BT549 cells. E Immunofluorescence assays of TRF2 and ?-H2AX in the indicated BT549 cells. Co-localizing events indicate telomere dysfunction induced foci (TIFs). The percentage of cells with more than 3 TIFs were analyzed. 100 cells were counted for each experiment. F Western blot analyses in BT549 cells as indicated. Quantification of Western blots is shown in Additional file 1: Fig. S5L. G Telomere-specific qPCR analysis to determine the relative telomere length in the indicated BT549 cells. H Western blot analyses in BT549 cells and MDA-MB-231 treated as indicated to examine the protein levels of TAZ and Rad51C. Quantification of Western blots is shown in Additional file 1: Fig. S5M. I Telomere-specific qPCR analysis to determine the relative telomere length in the indicated BT549 and MDA-MB-231 cells. J Southern analysis of TRFs in the indicated BT549 and MDA-MB-231 cells to determine the relative telomere length. Data are presented as mean ± SEM. At least three repeats were carried out for each test. Statistical analyses were performed with unpaired Student's t-test between two groups and one-way ANOVA followed by Tukey’s multiple-comparisons for multiple groups. NS, not significant, *p < 0.05, **p < 0.01, ***p < 0.001