An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea.
An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea.
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Orc1/Cdc6 直系同源物在古细菌 DNA 损伤反应中发挥着关键调节作用。
DOI：
10.1093/nar/gky487
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发表时间：
2018-07-27
影响因子：
14.9
通讯作者：
She Q
中科院分区：
文献类型：
--
作者：
Sun M;Feng X;Liu Z;Han W;Liang YX;She Q
虽然细菌和真核生物表现出不同的机制的DNA损伤反应（DDR）的监管，紫外线（UV）响应的表达在一些古细菌的调查没有产生任何确凿的证据古细菌DDR监管网络。然而，表达的Orc 1 -2，一个直系同源的古细菌起源识别复合物1/细胞分裂控制蛋白6（Orc 1/Cdc 6）超家族蛋白强烈激活硫磺硫化叶菌和硫化叶菌acidocaldarius紫外线照射后。本研究旨在探讨Orc 1 -2在冰岛硫化叶菌DNA损伤修复中的可能功能。对Δ orc 1 -2的DDR研究表明，Orc 1 -2缺陷消除了DNA损伤诱导的大量基因差异表达，突变体对DNA损伤处理表现出超敏反应。报告基因和DNA酶I足迹分析表明，Orc 1 -2相互作用与一个保守的六核苷酸基序存在于几个DDR基因启动子，并调节其表达。操纵orc 1 -2表达的启动子取代在这个古菌揭示了一个高水平的orc 1 -2的表达是必不可少的，但不足以触发DDR。总之，这些结果将Orc 1 -2置于古细菌DDR调节的中心，由此产生的以Orc 1 -2为中心的调节回路代表了在生命的第三领域--古生物中发现的第一个DDR网络。
While bacteria and eukaryotes show distinct mechanisms of DNA damage response (DDR) regulation, investigation of ultraviolet (UV)-responsive expression in a few archaea did not yield any conclusive evidence for an archaeal DDR regulatory network. Nevertheless, expression of Orc1-2, an ortholog of the archaeal origin recognition complex 1/cell division control protein 6 (Orc1/Cdc6) superfamily proteins was strongly activated in Sulfolobus solfataricus and Sulfolobus acidocaldarius upon UV irradiation. Here, a series of experiments were conducted to investigate the possible functions of Orc1-2 in DNA damage repair in Sulfolobus islandicus. Study of DDR in Δorc1-2 revealed that Orc1-2 deficiency abolishes DNA damage-induced differential expression of a large number of genes and the mutant showed hypersensitivity to DNA damage treatment. Reporter gene and DNase I footprinting assays demonstrated that Orc1-2 interacts with a conserved hexanucleotide motif present in several DDR gene promoters and regulates their expression. Manipulation of orc1-2 expression by promoter substitution in this archaeon revealed that a high level of orc1-2 expression is essential but not sufficient to trigger DDR. Together, these results have placed Orc1-2 in the heart of the archaeal DDR regulation, and the resulting Orc1-2-centered regulatory circuit represents the first DDR network identified in Archaea, the third domain of life.
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影响因子：
5.6
作者：
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通讯作者：
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影响因子：
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作者：
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模因套件：用于发现和搜索的工具。
影响因子：
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通讯作者：
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