DNA-mediated redox signaling for transcriptional activation of SoxR
DNA-mediated redox signaling for transcriptional activation of SoxR
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DOI：
10.1073/pnas.0906429106
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发表时间：
2009-08-11
影响因子：
11.1
通讯作者：
Barton, Jacqueline K.
中科院分区：
文献类型：
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作者：
Lee, Paul E.;Demple, Bruce;Barton, Jacqueline K.
在肠道细菌中，细胞对氧化应激的反应是通过氧化SoxR中的铁硫簇来激活的，然后诱导soxS的转录，打开一系列防御基因。在这里，我们证明在体外和细胞中，SoxR的激活可以发生在DNA介导的反应与鸟嘌呤自由基，氧化应激的早期基因组信号，作为氧化剂。发现其还原形式的SoxR通过修复鸟嘌呤自由基来抑制鸟嘌呤损伤。此外，用产生鸟嘌呤自由基的DNA结合光氧化剂处理的细胞促进soxS的表达。在体外，这种光氧化剂，拴在DNA 80 bp的soxS启动子，诱导转录激活SoxR照射后。因此，转录可以通过DNA介导的电荷传输从远处激活。这种化学反应为DNA介导的氧化应激信号传导提供了一般策略。
In enteric bacteria, the cellular response to oxidative stress is activated by oxidation of the iron-sulfur clusters in SoxR, which then induces transcription of soxS, turning on a battery of defense genes. Here we demonstrate both in vitro and in cells that activation of SoxR can occur in a DNA-mediated reaction with guanine radicals, an early genomic signal of oxidative stress, serving as the oxidant. SoxR in its reduced form is found to inhibit guanine damage by repairing guanine radicals. Moreover, cells treated with a DNA-binding photooxidant, which generates guanine radicals, promotes the expression of soxS. In vitro, this photooxidant, tethered to DNA 80 bp from the soxS promoter, induces transcription by activating SoxR upon irradiation. Thus, transcription can be activated from a distance through DNA-mediated charge transport. This chemistry offers a general strategy for DNA-mediated signaling of oxidative stress.