Fig. 1: Top1-dependent deletions in S. cerevisiae resemble ID4, a cancer mutational signature of unknown aetiology.
From: Signatures of TOP1 transcription-associated mutagenesis in cancer and germline
a, The ID4 signature comprises small deletions (typically 2, 3 or 4 bp in size) of one repeat unit at SSTR and MH sites. Repeated sequences (i–vi) are shown in bold and colour. Deletions are shown in red. b, Indel mutations similar to those detected in ID4 accumulate genome-wide in yeast with high levels of genome-embedded ribonucleotides. Reanalysis of WGS data for rnh201∆ pol2-M644G yeast25. c, Schematic of a frameshift mutation reporter containing many 2 bp SSTRs. Frameshift mutations in HygroR result in neomycin-resistant yeast colonies. PTEF, TEF promoter; P2A, self-cleaving peptide. d, e, Fluctuation assays demonstrated that Top1-mediated 2 bp SSTR mutations occur in wild-type and RNase-H2-deficient (rnh201∆) backgrounds. d, Mutation rates for n = 16 independent cultures per strain. Data are median ± 95% confidence intervals. e, WT and rnh201Δ have similar indel mutation spectra, and differ from top1Δ strains. Spectra of neomycin-resistant colonies. n indicates the number of independent indels detected. Cosine similarity P values were empirically determined (Extended Data Fig. 2e, f). Del, deletion; ins, insertion.
