Synthetic circuit identifies subpopulations with sustained memory of DNA damage
Synthetic circuit identifies subpopulations with sustained memory of DNA damage
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DOI：
10.1101/gad.1994911
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发表时间：
2011-03-01
影响因子：
10.5
通讯作者：
Silver, Pamela A.
中科院分区：
文献类型：
--
作者：
Burrill, Devin R.;Silver, Pamela A.
对刺激的不同反应会影响细胞如何死于疾病。在酵母中，DNA 损伤会产生异质反应。为了描述反应如何影响细胞的未来行为，我们构建了一个基于转录的记忆电路，可以检测 DNA 修复，以分离具有可遗传损伤反应的亚群。强烈反应的细胞表现出多代效应，包括生长缺陷和铁相关基因表达。反应较弱的细胞表现出突变频率增加，但恢复野生型行为。这两个亚群在多代人中仍然存在差异，表明损伤记忆是可遗传的。总的来说，这项工作证明了使用合成生物学来定义环境暴露如何影响不同细胞命运的有效性。
Differential responses to stimuli can affect how cells succumb to disease. In yeast, DNA damage can create heterogeneous responses. To delineate how a response contributes to a cell's future behavior, we constructed a transcription-based memory circuit that detects DNA repair to isolate subpopulations with heritable damage responses. Strongly responsive cells show multigenerational effects, including growth defects and iron-associated gene expression. Less-responsive cells exhibit increased mutation frequencies but resume wild-type behavior. These two subpopulations remain distinct for multiple generations, indicating a transmissible memory of damage. Collectively, this work demonstrates the efficacy of using synthetic biology to define how environmental exposure contributes to distinct cell fates.