Distinguishing preferences of human APOBEC3A and APOBEC3B for cytosines in hairpin loops, and reflection of these preferences in APOBEC-signature cancer genome mutations.

The APOBEC3 enzymes convert cytosines in single-stranded DNA to uracils to protect against viruses and retrotransposons but can contribute to mutations that diversify tumors. To understand the mechanism of mutagenesis, we map the uracils resulting from expression of APOBEC3B or its catalytic carboxy-terminal domain (CTD) in Escherichia coli. Like APOBEC3A, the uracilomes of A3B and A3B-CTD show a preference to deaminate cytosines near transcription start sites and the lagging-strand replication templates and in hairpin loops.

Distinguishing preferences of human APOBEC3A and APOBEC3B for cytosines in hairpin loops, and reflection of these preferences in APOBEC-signature cancer genome mutations.

The APOBEC3 family of enzymes convert cytosines in single-stranded DNA to uracils thereby causing mutations. These enzymes protect human cells against viruses and retrotransposons, but in many cancers they contribute to mutations that diversify the tumors and help them escape anticancer drug treatments. To understand the mechanism of mutagenesis by APOBEC3B, we expressed the complete enzyme or its catalytic carboxy-terminal domain (CTD) in repair-deficient and mapped the resulting uracils using uracil pull-down and sequencing technology.