State Key Laboratory of Agricultural Microbiology and College of Life Science and Technology, Huazhong Agricultural University, 430070 Wuhan, China.
Archaea Centre, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
Nucleic Acids Res. 2018 Aug 21;46(14):7085-7096. doi: 10.1093/nar/gky236.
Previously it was shown that UV irradiation induces a strong upregulation of tfb3 coding for a paralog of the archaeal transcriptional factor B (TFB) in Sulfolobus solfataricus, a crenarchaea. To investigate the function of this gene in DNA damage response (DDR), tfb3 was inactivated by gene deletion in Sulfolobus islandicus and the resulting Δtfb3 was more sensitive to DNA damage agents than the original strain. Transcriptome analysis revealed that a large set of genes show TFB3-dependent activation, including genes of the ups operon and ced system. Furthermore, the TFB3 protein was found to be associated with DDR gene promoters and functional dissection of TFB3 showed that the conserved Zn-ribbon and coiled-coil motif are essential for the activation. Together, the results indicated that TFB3 activates the expression of DDR genes by interaction with other transcriptional factors at the promoter regions of DDR genes to facilitate the formation of transcription initiation complex. Strikingly, TFB3 and Ced systems are present in a wide range of crenarchaea, suggesting that the Ced system function as a primary DNA damage repair mechanism in Crenarchaeota. Our findings further suggest that TFB3 and the concurrent TFB1 form a TFB3-dependent DNA damage-responsive circuit with their target genes, which is evolutionarily conserved in the major lineage of Archaea.
先前的研究表明，紫外线照射会强烈诱导编码古菌转录因子 B（TFB）的 paralog 的 tfb3 在嗜热酸菌 Sulfolobus solfataricus 中上调。为了研究该基因在 DNA 损伤反应（DDR）中的功能，我们通过基因缺失使 Sulfolobus islandicus 中的 tfb3 失活，结果表明，与原始菌株相比，缺失 tfb3 的菌株对 DNA 损伤剂更敏感。转录组分析显示，大量基因显示出 TFB3 依赖性激活，包括 ups 操纵子和 ced 系统的基因。此外，发现 TFB3 蛋白与 DDR 基因启动子相关，TFB3 的功能分析表明，保守的 Zn-ribbon 和 coiled-coil 基序对于激活是必需的。总之，这些结果表明，TFB3 通过与 DDR 基因启动子区域的其他转录因子相互作用，激活 DDR 基因的表达，从而促进转录起始复合物的形成。引人注目的是，TFB3 和 Ced 系统广泛存在于古菌中，表明 Ced 系统在古菌中作为一种主要的 DNA 损伤修复机制发挥作用。我们的研究结果进一步表明，TFB3 和同时存在的 TFB1 与它们的靶基因一起形成了一个 TFB3 依赖性的 DNA 损伤反应回路，该回路在古菌的主要谱系中具有进化保守性。
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