Genome-wide surveillance of transcription errors in response to genotoxic stress
Genome-wide surveillance of transcription errors in response to genotoxic stress
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DOI：
10.1073/pnas.2004077118
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发表时间：
2021-01-05
影响因子：
11.1
通讯作者：
Vermulst, M.
中科院分区：
文献类型：
--
作者：
Fritsch, C.;Gout, J-F;Vermulst, M.
诱变化合物是人类疾病的一个潜在来源。通过诱导遗传不稳定，它们可以加速人类癌症的进化或导致遗传疾病的发展。在这里，我们表明，除了基因突变，诱变剂也是转录错误的一个强大来源。这些错误出现在分裂和不分裂的细胞中，影响细胞内的每一类转录本，在某些情况下，远远超过基因组中出现的突变数量。此外，我们揭示了转录错误对诱变剂暴露的响应动力学，并发现DNA修复是必要的，以减轻暴露后的转录突变。综上所述，这些观察结果对我们理解人类衰老和疾病中的突变具有深远的影响，并表明DNA损伤对人类生理的影响被大大低估。
Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors arise in dividing and nondividing cells alike, affect every class of transcripts inside cells, and, in certain cases, greatly exceed the number of mutations that arise in the genome. In addition, we reveal the kinetics of transcription errors in response to mutagen exposure and find that DNA repair is required to mitigate transcriptional mutagenesis after exposure. Together, these observations have far-reaching consequences for our understanding of mutagenesis in human aging and disease, and suggest that the impact of DNA damage on human physiology has been greatly underestimated.