University of Southern California, Leonard Davis School of Gerontology, Los Angeles, CA, USA.
Translational Research Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Nucleic Acids Res. 2024 Sep 9;52(16):e76. doi: 10.1093/nar/gkae632.
Our genome is exposed to a wide variety of DNA-damaging agents. If left unrepaired, this damage can be converted into mutations that promote carcinogenesis or the development of genetically inherited diseases. As a result, researchers and clinicians require tools that can detect DNA damage and mutations with exceptional sensitivity. In this study, we describe a massively parallel sequencing tool termed Mutation And DNA Damage Detection-seq (MADDD-seq) that is capable of detecting O6-methyl guanine lesions and mutations simultaneously, with a single assay. To illustrate the dual capabilities of MADDD-seq, we treated WT and DNA repair deficient yeast cells with the DNA-damaging agent MNNG and tracked DNA lesions and mutations over a 24-h time period. This approach allowed us to identify thousands of DNA adducts and mutations in a single sequencing run and gain deep insight into the kinetics of DNA repair and mutagenesis.
我们的基因组会暴露于各种类型的 DNA 损伤试剂中。如果这些损伤得不到修复，就可能会转化为促进癌变或遗传疾病发展的突变。因此，研究人员和临床医生需要能够以极高的灵敏度检测 DNA 损伤和突变的工具。在这项研究中，我们描述了一种名为“突变和 DNA 损伤检测测序（Mutation And DNA Damage Detection-seq，MADDD-seq）”的大规模平行测序工具，该工具能够在单个检测中同时检测 O6-甲基鸟嘌呤损伤和突变。为了说明 MADDD-seq 的双重功能，我们用 DNA 损伤试剂 MNNG 处理 WT 和 DNA 修复缺陷型酵母细胞，并在 24 小时的时间内追踪 DNA 损伤和突变。这种方法使我们能够在单个测序运行中鉴定数千个 DNA 加合物和突变，并深入了解 DNA 修复和诱变的动力学。
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