Characterisation of the spectrum and genetic dependence of collateral mutations induced by translesion DNA synthesis
Fig 5
Collateral mutagenesis greatly contributes to overall mutational burden.
(A) Scheme of solitary collateral mutations. Collateral mutations can occur in pairs with primary events during erroneous bypass (upper row) or downstream of correctly bypassed lesions (bottom row). (B) Occurrences of CC and GG dinucleotides around non-primary, solitary mutations in all cisplatin treated DT40 samples show an overrepresentation of potential lesion sites. The black lines connect dinucleotide counts in each position in a +/- 300 bps window, with lowess smoothing indicated in red. (C) The five components identified by de novo NMF on cisplatin-treated, UVC-treated and HR-deficient DT40 samples with mutations in close pairs treated as separate samples. (D) Relative contributions of the components in panel (C). Mutations in close pairs, denoted by red dots and wider columns, were separated in each genotype-treatment interaction, and treated as a distinct sample. (E) Contribution of Sig_CM to the mutation sets of cisplatin-treated samples of the indicated genotypes deconstructed using Sig_Cisp_1, Sig_Cisp_2, Sig_CM and Sig_BG/HRD. Statistical significance is indicated (two-sided unpaired t-test).