单链DNA胞嘧啶脱氨酶APOBEC3B 是一种参与癌症的抗病毒蛋白。然而，其在细胞中的底物还不完全明确。本文通过APOBEC3B蛋白组学研究发现其与意外数量的R-环因子有相互作用。生物化学实验显示APOBEC3B与细胞和体外中的R-环结合。遗传实验表明缺乏APOBEC3B的细胞中R-环增加，APOBEC3B过表达的细胞中R-环减少。基因组广泛分析显示在生理和刺激诱导下的R-环整体动态发生了重大变化，成千上万个不同变化的区域，同时发现APOBEC3B结合了其中许多位点。APOBEC3突变影响了肿瘤中过表达的基因和剪接因子突变的肿瘤，而APOBEC3相关的扩增作用具有与APOBEC3B脱氨相关的RTCW模体富集性。综上所述，由于APOBEC3B结合单链DNA和RNA并且优先对DNA进行脱氨，这些结果支持了APOBEC3B在调控R-环并在癌症中促进R-环突变的机制。 © 2023. 作者。

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions, as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts genes overexpressed in tumors and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW motifs consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B regulates R-loops and contributes to R-loop mutagenesis in cancer.© 2023. The Author(s).