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. Author manuscript; available in PMC: 2017 Jan 20.
Published in final edited form as: Nature. 2016 Jul 20;535(7612):382–387. doi: 10.1038/nature18325

Figure 4. Replication fork protection confers genome stability and chemotherapeutic resistance.

Figure 4

(a-b) Genomic instability measured in metaphase spreads from B cells (n=50; ns, not significant, *P ≤ 0.05, ** P ≤ 0.01, *** P ≤ 0.001,****P ≤ 0.0001, Unpaired t-test). Experiments were repeated 4 times. (c) Ratio of IdU vs. CldU in BRCA2-mutated PEO1 cells either mock (shNSC) infected or infected with shRNA against CHD4 (shCHD4). (ns, not significant, *P ≤ 0.05, ****P ≤ 0.0001, Mann-Whitney test). 125 replication forks were analyzed. (d) Ratio of IdU vs. CldU in HU-treated B cells. (ns, not significant, *P ≤ 0.05, ****P ≤ 0.0001, Mann-Whitney test). 125 replication forks were analyzed. (e) Genomic instability in B cells (n=50; ns, not significant, *** P ≤ 0.001, Unpaired t-test). Experiments repeated 4 times. (f-g) Kaplan-Meier survival curves in mice implanted with either PARPi-naïve or -resistant tumors and treated with either topotecan (f) or cisplatin (g) using Log-rank (Mantel-Cox) test. (h) Ratio of IdU vs. CldU in untreated or HU-treated tumors (PARPi naive vs. PARPi resistant). (ns, not significant, ****P ≤ 0.0001, Mann-Whitney test). 125 replication forks were analyzed.