Fig. 1: TLS plays a role in spontaneous mutagenesis in BRCA1 deficient cells.

The mean number of newly arising SBS (single base substitution, a), insertion (b) and deletion (c) mutations detected in DT40 cell clones of the indicated genotypes following 50 days of culturing an ancestral clone. Error bars indicate standard error of the mean (SEM), individual values are also shown with red symbols. The significance of tested differences is shown (ns not significant, unpaired two-sided t-test, n = 3 biologically independent samples except n = 6 for BRCA1^–/– cells). d Deconstruction of the averaged spontaneous triplet SBS spectra of the indicated genotypes into three mutational signatures using non-negative matrix factorisation. The inset shows cosine similarities to published triplet signatures, see text for details. e Triplet spectra of the mutational signatures derived in (d). Each mutation class, as indicated at the top of the panel, is separated into 16 categories based on the identity of the preceding and following nucleotide as shown below. The order of the following nucleotides, not shown due to lack of space, is alphabetical. f POLK expression level in all PCAWG stomach adenocarcinoma samples with RNAseq data, grouped according to whether >5% contribution of SBS.POLKΔ was detected in a deconstruction of the somatic mutation spectrum to all COSMIC v3 SBS signatures. g The summed contribution of COSMIC triplet signatures SBS17a and SBS17b to the somatic mutation spectrum in all PCAWG oesophagus or stomach adenocarcinoma samples, grouped according to SBS.POLKΔ contribution as in (f). The mean, upper and lower quartiles are shown in (f) and (g), statistical significances are indicated (Wilcoxon rank-sum test). Source data are provided as a Source Data file.