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APOBEC mutagenesis is low in most types of non-B DNA structures


ABSTRACT: Summary While somatic mutations are known to be enriched in genome regions with non-canonical DNA secondary structure, the impact of particular mutagens still needs to be elucidated. Here, we demonstrate that in human cancers, the APOBEC mutagenesis is not enriched in direct repeats, mirror repeats, short tandem repeats, and G-quadruplexes, and even decreased below its level in B-DNA for cancer samples with very high APOBEC activity. In contrast, we observe that the APOBEC-induced mutational density is positively associated with APOBEC activity in inverted repeats (cruciform structures), where the impact of cytosine at the 3’-end of the hairpin loop is substantial. Surprisingly, the APOBEC-signature mutation density per TC motif in the single-stranded DNA of a G-quadruplex (G4) is lower than in the four-stranded part of G4 and in B-DNA. The APOBEC mutagenesis, as well as the UV-mutagenesis in melanoma samples, are absent in Z-DNA regions, owing to the depletion of their mutational signature motifs. Graphical abstract Highlights • APOBEC mutagenesis is not enriched in most non-canonical DNA structures• Inverted repeats (cruciform structures) show increased APOBEC mutagenesis• G-quadruplex’s unstructured strand has low APOBEC-induced mutation density• Decrease of APOBEC mutagenesis in non-B DNA possibly associated with PrimPol Cancer; Cancer mutagenesis.

SUBMITTER: Ponomarev G 

PROVIDER: S-EPMC9213766 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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