杂环芳香胺（HAAs）是在烧烤肉类和香烟烟雾中发现的强致癌物质。然而，目前只鉴定出了少数真核细胞抗性基因。我们利用酿酒酵母（Saccharomyces cerevisiae）来鉴定能够赋予对2-氨基-3-甲基咪唑[4,5-f]苯并喹啉（IQ）的抗性的基因。CYP1A2和NAT2可以将IQ激活成致突变的亚硝基化合物。我们对表达人类CYP1A2和NAT2基因或无人类基因的删减文库进行了暴露实验，暴露浓度为400或800 μM IQ，且实验持续五代或十代。我们使用Illumina HiSeq 2500平台对DNA条形码进行了测序，针对完全匹配的条形码进行了统计学显著性分析。在"人源化"文库的IQ抗性筛选中，我们鉴定了424个ORFs，其中包括337个已知功能基因。对于51个基因的选择性验证，我们使用了生长曲线、竞争生长或尝试蓝染色实验。在不表达人类基因的文库中，鉴定了143个对IQ自身具有抗性的ORFs。核糖体蛋白和蛋白修饰基因在原始和"人源化"文库中均被确定为IQ抗性基因，而氮代谢、DNA修复和生长控制基因也在"人源化"文库中明显。我们还鉴定了包括酪蛋白激酶2（CK2）和组蛋白伴侣蛋白质复合体（HIR）在内的蛋白质复合体。在DNA修复和检查点基因中，我们鉴定了参与后复制修复（RAD18，UBC13，REV7）、碱基切割修复（NTG1）和检查点信号传导（CHK1，PSY2）的基因。这些研究强调了核糖体蛋白基因在赋予IQ抗性中的作用，并阐明了赋予活化的IQ抗性的DNA修复途径。© 2023 作者。由牛津大学出版社代表遗传学学会发表。

Heterocyclic aromatic amines (HAAs) are potent carcinogenic agents found in charred meats and cigarette smoke. However, few eukaryotic resistance genes have been identified. We used Saccharomyces cerevisiae (budding yeast) to identify genes that confer resistance to 2-amino-3-methylimidazo[4,5-f] quinoline (IQ). CYP1A2 and NAT2 activate IQ to become a mutagenic nitrenium compound. Deletion libraries expressing human CYP1A2 and NAT2 or no human genes were exposed to either 400 or 800 µM IQ for five or ten generations. DNA barcodes were sequenced using the Illumina HiSeq 2500 platform and statistical significance was determined for exactly matched barcodes. We identified 424 ORFs, including 337 genes of known function, in duplicate screens of the "humanized" collection for IQ resistance; resistance was further validated for a select group of 51 genes by growth curves, competitive growth, or trypan blue assays. Screens of the library not expressing human genes identified 143 ORFs conferring resistance to IQ per se. Ribosomal protein and protein modification genes were identified as IQ resistance genes in both the original and "humanized" libraries, while nitrogen metabolism, DNA repair, and growth control genes were also prominent among the "humanized" library. Protein complexes identified included the casein kinase 2 (CK2) and histone chaperone (HIR) complex. Among DNA Repair and checkpoint genes, we identified those that function in post-replication repair (RAD18, UBC13, REV7), base excision repair (NTG1), and checkpoint signaling (CHK1, PSY2). These studies underscore the role of ribosomal protein genes in conferring IQ resistance, and illuminate DNA repair pathways for conferring resistance to activated IQ.© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.