Extended Data Fig. 5: Structure-forming repeats in MSI cells activate ATR.
From: Repeat expansions confer WRN dependence in microsatellite-unstable cancers
a, Genome browser screenshot displaying END-seq profiles for DMSO-treated KM12, HCT116, SW837 and RPE-1 cells containing an inducible shWRN cassette processed in situ with purified recombinant MUS81–EME1. Cells are indicated as MSI (red) or MSS (blue, n = 1). b, Quantification of END-seq peak intensity for libraries displayed in a. Box plots are as in Fig. 2a, b. c, Western blot analysis of WRN and pKAP1 levels in HCT116 cells expressing wild-type WRN, or ATR phosphorylation mutants WRN(3A) or WRN(6A). Endogenous WRN was depleted using an siRNA targeting the WRN 5′ UTR. Data are representative of three independent experiments. For gel source data, see Supplementary Fig. 1. d, Genome browser screenshot displaying END-seq profiles within FRA3B on chromosome 3 as normalized read density (RPM) for KM12-shWRN, HCT116-shWRN, RPE-1-shWRN, and eHAP-shWRN cells treated with doxycycline (shWRN) for 72 h or APH plus ATRi for 8 h. e, Venn diagrams displaying overlap of DSBs detected after WRN depletion or APH plus ATRi treatment in KM12 and HCT116 cells. n = 1,000 random datasets were generated to test significance of overlap using one-sided Fisher’s exact test for both the Venn diagrams (P < 2.2 × 10−16).
