Mfd is required for rapid recovery of transcription following UV-induced DNA damage but not oxidative DNA damage in Escherichia coli.
Mfd is required for rapid recovery of transcription following UV-induced DNA damage but not oxidative DNA damage in Escherichia coli.
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Mfd 是紫外线诱导的 DNA 损伤后转录快速恢复所必需的，但大肠杆菌中的氧化性 DNA 损伤则不需要 Mfd。
DOI：
10.1128/jb.06725-11
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发表时间：
2012
影响因子：
3.2
通讯作者：
Courcelle,Justin
中科院分区：
文献类型：
--
作者：
Schalow,BrandyJ;Courcelle,CharmainT;Courcelle,Justin
转录偶联修复 (TCR) 是一种细胞过程，通过该过程，活性基因的转录链比非转录链或整个基因组修复某些形式的 DNA 损伤的速度更快。在人类中，TCR 耦合因子 CSB 在 UV 诱导和氧化 DNA 损伤后恢复转录方面发挥着关键作用。它还间接有助于某些形式的氧化 DNA 损伤的整体修复。大肠杆菌同系物 Mfd 对于紫外线引起的损伤的 TCR 来说同样是必需的。然而，其对转录恢复和氧化损伤整体修复的贡献尚未得到检验。在此，我们报告了首次对大肠杆菌中紫外线诱导和氧化 DNA 损伤后转录恢复的直接研究。我们观察到 mfdoruvr 中的突变降低了紫外线诱导损伤后转录恢复的速度。相比之下，在氧化损伤后，相对于野生型细胞，mfd、uvrA、fpg、nth、orpolB dinB umuDC 突变体的转录恢复率没有检测到差异。mfd 突变体还完全抵抗过氧化氢 (H2O2)，并以与野生型细胞相当的速度从基因组中去除氧化损伤。结果表明，Mfd 促进大肠杆菌中紫外线诱导损伤后基因表达的快速恢复。此外，这些发现意味着 Mfd 可能在功能上不同于其人类 CSB 同源物，因为它没有明显有助于氧化损伤后基因表达的恢复或整体修复。
Transcription-coupled repair (TCR) is a cellular process by which some forms of DNA damage are repaired more rapidly from transcribed strands of active genes than from nontranscribed strands or the overall genome. In humans, the TCR coupling factor, CSB, plays a critical role in restoring transcription following both UV-induced and oxidative DNA damage. It also contributes indirectly to the global repair of some forms of oxidative DNA damage. The Escherichia coli homolog, Mfd, is similarly required for TCR of UV-induced lesions. However, its contribution to the restoration of transcription and to global repair of oxidative damage has not been examined. Here, we report the first direct study of transcriptional recovery following UV-induced and oxidative DNA damage in E. coli. We observed that mutations inmfdoruvrAreduced the rate that transcription recovered following UV-induced damage. In contrast, no difference was detected in the rate of transcription recovery inmfd,uvrA,fpg,nth, orpolB dinB umuDCmutants relative to wild-type cells following oxidative damage.mfdmutants were also fully resistant to hydrogen peroxide (H2O2) and removed oxidative lesions from the genome at rates comparable to wild-type cells. The results demonstrate that Mfd promotes the rapid recovery of gene expression following UV-induced damage in E. coli. In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.