Extended Data Fig. 6: (TA)n repeat sequences are underrepresented in whole-genome sequencing data from MSI cells.
From: Repeat expansions confer WRN dependence in microsatellite-unstable cancers
a, Bar plots indicating the percentage of recurrent mutations in different classes of repeats (left; mono, di, tri and tetra) and a bar plot (right) showing the number of various dinucleotide repeats in the 1,000 altered loci. The plots were based on sequencing analysis from24, which considered microsatellites smaller than 40 bp. b, Agarose gels showing PCR fragments (or lack thereof) of sites of different (TA)n repeats in one MSS and four MSI cell lines. Broken sites B1–B8 were chosen based on the presence of END-seq peaks after WRN depletion in KM12 cells. Sites NB1–NB3 were chosen with similar (TA)− repeat lengths as broken sites, but were not broken after WRN depletion in KM12 cells. Fragment sizes (in bp) are displayed. Data are representative of three independent experiments. For gel source data, see Supplementary Fig. 1. c, Genome browser screenshots of short read PCR-free whole genome sequencing reads, indicating coverage, in KM12 and HCT116 cell lines (n = 1). Shown are two regions containing (TA)n repeats, one that displays END-seq peaks after WRN depletion in KM12 (site B2), and one that does not (site NB3). Regions correspond to equivalent PCR sites in Fig. 4a and Extended Data Fig. 5b. d, Box plots displaying coverage at different classes of mono- and di-nucleotide repeats in PCR-free whole-genome sequencing libraries made from HCT116 cells. (TA)n repeats are split into those that overlap END-seq peaks after shWRN induction, and those that do not contain DSBs. Dotted red lines indicate the average coverage over the genome.
