DNA-mediated signaling by proteins with 4Fe-4S clusters is necessary for genomic integrity.
DNA-mediated signaling by proteins with 4Fe-4S clusters is necessary for genomic integrity.
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DOI：
10.1021/ja501973c
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发表时间：
2014-04-30
影响因子：
15
通讯作者：
Barton, Jacqueline K.
中科院分区：
文献类型：
--
作者：
Grodick, Michael A.;Segal, Helen M.;Zwang, Theodore J.;Barton, Jacqueline K.
铁硫簇越来越多地被发现与参与DNA加工的酶有关。在这里，我们描述了这些氧化还原簇在DNA介导的电荷传输信号在大肠杆菌中的作用。不同途径的DNA修复蛋白之间的差异。DNA修饰的电化学表明，4Fe-4S簇的DNA结合的DinG，ATP依赖性解旋酶，修复R环，是氧化还原活性在细胞电位和ATP水解增加DNA介导的氧化还原信号。原子力显微镜实验表明，DinG和核酸内切酶III（EndoIII），碱基切除修复酶，合作在长距离使用DNA电荷传输重新分配到DNA损伤的区域。此外，遗传学实验表明，这种DNA介导的蛋白质之间的信号传导也发生在细胞内，并且值得注意的是，在应激条件下细胞活力是必需的。在大肠杆菌菌株中沉默编码EndoIII的基因。其中DinG修复是必需的大肠杆菌导致显著的生长缺陷，其通过与EndoIII互补而不是与具有酶活性但不能进行DNA电荷转运的EndoIII突变体互补来挽救。因此，这项工作阐明了一个基本的机制，以协调整个基因组的DNA修复酶的活动。
Iron–sulfur clusters have increasingly been found to be associated with enzymes involved in DNA processing. Here we describe a role for these redox clusters in DNA-mediated charge-transport signaling in E. coli between DNA repair proteins from distinct pathways. DNA-modified electrochemistry shows that the 4Fe–4S cluster of DNA-bound DinG, an ATP-dependent helicase that repairs R-loops, is redox-active at cellular potentials and ATP hydrolysis increases DNA-mediated redox signaling. Atomic force microscopy experiments demonstrate that DinG and Endonuclease III (EndoIII), a base excision repair enzyme, cooperate at long-range using DNA charge transport to redistribute to regions of DNA damage. Genetics experiments, moreover, reveal that this DNA-mediated signaling among proteins also occurs within the cell and, remarkably, is required for cellular viability under conditions of stress. Silencing the gene encoding EndoIII in a strain of E. coli where repair by DinG is essential results in a significant growth defect that is rescued by complementation with EndoIII but not with an EndoIII mutant that is enzymatically active but unable to carry out DNA charge transport. This work thus elucidates a fundamental mechanism to coordinate the activities of DNA repair enzymes across the genome.
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影响因子：
4.7
作者：
Gorodetsky, Alon A.;Buzzeo, Marisa C.;Barton, Jacqueline K.
通讯作者：
Barton, Jacqueline K.
影响因子：
14.9
作者：
Dunn AR;Kad NM;Nelson SR;Warshaw DM;Wallace SS
通讯作者：
Wallace SS
影响因子：
15
作者：
Pheeney, Catrina G.;Arnold, Anna R.;Grodick, Michael A.;Barton, Jacqueline K.
通讯作者：
Barton, Jacqueline K.
影响因子：
2.9
作者：
CUNNINGHAM, RP;ASAHARA, H;EMPTAGE, MH
通讯作者：
EMPTAGE, MH
影响因子：
56.9
作者：
Gari, Kerstin;Ortiz, Ana Maria Leon;Boulton, Simon J.
通讯作者：
Boulton, Simon J.