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

Ponomarev, Gennady V. and Fatykhov, Bulat and Nazarov, Vladimir A. and Abasov, Ruslan and Shvarov, Evgeny and Landik, Nina Vicky and Denisova, Alexandra A. and Chervova, Almira A. and Gelfand, Mikhail S. and Kazanov, Marat (2022) APOBEC mutagenesis is low in most types of non-B DNA structures. iScience, 25 (7). ISSN 2589-0042

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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.
Item Type: Article
Uncontrolled Keywords: cancer; cancer mutagenesis
Divisions: Faculty of Engineering and Natural Sciences
Depositing User: Marat Kazanov
Date Deposited: 21 Aug 2022 20:23
Last Modified: 21 Aug 2022 20:23
URI: https://research.sabanciuniv.edu/id/eprint/44219

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