Fig. 7: Inhibition of XPF suppresses cell proliferation in ALT cells.

a Telomere length measured by TRF analysis in cells after prolonged XPF-depletion for 8 weeks in U2OS cells. The same amount of DNA as TRF assay was loaded in the EtBr gel. The mean of telomere length was quantified (top-right) from three independent knockdown experiments. P-values by two-tailed Student’s t-test. Bars, mean ± SEM. b Cell proliferation assay after XPF knockdown in U2OS, HeLa, and WI38-VA cells. Bars, mean ± SD. P-values by two-way ANOVA. ns, no significance. Representative of four independent experiments. Other replicates show similar trends and are provided in the Source Data file. c Cell survival rates after the 3-day treatment of XPF-ERCC1 inhibitor (NSC130813), doxorubicin, etoposide, and cisplatin in ALT + (U2OS) and ALT- (HeLa) cells. P-values by two-way ANOVA. Bars, mean ± SD. At least three independent experiments were averaged. d Model of TERRA and XPF promoting break-induced telomere synthesis in ALT cells. TERRA promotes APB and R-loop formation at telomeres. XPF and XPG are recruited by TERRA R-loops to generate DNA double-strand breaks at ALT telomeres, thus facilitating HR and strand invasion to initiate break-induced telomere synthesis.