Action-at-a-distance mutations induced by 8-oxo-7,8-dihydroguanine are dependent on APOBEC3

Fukushima Ruriko

Suzuki Tetsuya

Kobayakawa Akari

Kamiya Hiroyuki

Mutagenesis

DNA oxidation is a serious threat to genome integrity and is involved in mutations and cancer initiation. The G base is most frequently damaged, and 8-oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) is one of the predominant damaged bases. In human cells, GO causes a G:C→T:A transversion mutation at the modified site, and also induces untargeted substitution mutations at the G bases of 5ʹ-GpA-3ʹ dinucleotides (action-at-a-distance mutations). The 5ʹ-GpA-3ʹ sequences are complementary to the 5ʹ-TpC-3ʹ sequences, the preferred substrates for apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) cytosine deaminases, and thus their contribution to mutagenesis has been considered. In this study, APOBEC3B, the most abundant APOBEC3 protein in human U2OS cells, was knocked down in human U2OS cells, and a GO-shuttle plasmid was then transfected into the cells. The action-at-a-distance mutations were reduced to ~25% by the knockdown, indicating that GO-induced action-at-a-distance mutations are highly dependent on APOBEC3B in this cell line.

8-oxo-7

8-dihydroguanine

8-hydroxyguanine

action-at-a-distance mutation

APOBEC3

cytosine deaminase

eng

Oxford

This is a pre-copyedited, author-produced version of an article accepted for publication in Mutagenesis following peer review. The version of record Mutagenesis, Volume 39, Issue 1, January 2024, Pages 24–31 is available online at: https://doi.org/10.1093/mutage/gead023.

This is not the published version. Please cite only the published version.

この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。

[DOI] https://doi.org/10.1093/mutage/gead023 isVersionOf

日本学術振興会

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日本学術振興会

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