BACKGROUND & AIMS: :Gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO2 NPs) are widely used in cosmetic products such as preservatives, colorants and sunscreens. This study investigated the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest with Escherichia coli PQ37. The maximum exposure concentrations for each nanoparticle were 3.23 mg l(-1) for Au NPs, 32.3 mg l(-1) for Ag NPs and 100 mg l(-1) for ZnO NPs and TiO2 NPs. Additionally, in order to compare the genotoxicity of nanoparticles and corresponding dissolved ions, the ions were assessed in the same way as nanoparticles. The genotoxicity of the titanium ion was not assessed because of the extremely low solubility of TiO2 NPs. Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn, in a range of tested concentrations, exerted no effects in the SOS chromotest, evidenced by maximum IF (IFmax) values of below 1.5 for all chemicals. Owing to the results, nanosized Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn are classified as non-genotoxic on the basis of the SOS chromotest used in this study. To the best of our knowledge, this is the first study to evaluate the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest.

背景与目标： ：金纳米颗粒（Au NPs），银纳米颗粒（Ag NPs），氧化锌纳米颗粒（ZnO NPs）和二氧化钛纳米颗粒（TiO2 NPs）广泛用于化妆品，如防腐剂，着色剂和防晒霜。这项研究使用大肠杆菌PQ37进行SOS色度测试，研究了金纳米粒子，银纳米粒子，锌纳米粒子和二氧化钛纳米粒子的遗传毒性。纳米金的最大暴露浓度分别为：金纳米颗粒为3.23μg-1（-1），银纳米颗粒为32.3μg-1（-1），锌纳米颗粒和二氧化钛纳米颗粒的最大暴露浓度为100μg-1（-1）。另外，为了比较纳米粒子和相应溶解离子的遗传毒性，以与纳米粒子相同的方式评估离子。由于TiO2 NPs的溶解度极低，因此未评估钛离子的遗传毒性。在各种测试浓度范围内，Au NPs，Ag NPs，ZnO NPs，TiO2 NPs和Au，Ag和Zn离子对SOS色度测试均无影响，所有化学药品的最大IF（IFmax）值均低于1.5证明了这一点。由于该结果，根据本研究中使用的SOS色度测试，将纳米级的Au NPs，Ag NPs，ZnO NPs，TiO2 NPs以及Au，Ag和Zn的离子归类为非遗传毒性。据我们所知，这是第一项使用SOS色度分析评估Au NPs，Ag NPs，ZnO NPs和TiO2 NPs的遗传毒性的研究。

BACKGROUND & AIMS: :DNA damage-induced SOS response elicits the induction of cell-division suppressor as well as DNA repair genes. In Gram-positive bacteria, cell-division suppressor genes, so far characterized from Bacillus subtilis (yneA) and Mycobacterium tuberculosis (rv2719c), share limited homology, but are both located in the vicinity of lexA on their respective genomes. Using this proximity to lexA, Corynebacterium glutamicum R divS (cgR1759) was identified as an SOS-inducible cell-division suppressor in this study. The amino acid sequence of DivS showed no homology to that of YneA and Rv2719c. divS expression was markedly induced by DNA-damaging mitomycin C treatment in wild-type cells, but not in its DeltarecA mutant cells, which are unable to induce the SOS response. Wild-type C. glutamicum R cells exposed to DNA-damaging mitomycin C exhibited elongated morphology that, using green fluorescent protein-FtsZ fusion protein, was attributed to defects in FtsZ ring assembly. Cells defective in FtsZ ring assembly were subsequently incapable of septum wall synthesis. In the presence of mitomycin C, divS mutant cells did not exhibit this elongated morphology, whereas cells overexpressing divS were elongated and abnormally branched.

背景与目标： DNA损伤诱导的SOS反应引发细胞分裂抑制因子以及DNA修复基因的诱导。在革兰氏阳性细菌中，到目前为止，以枯草芽孢杆菌（yneA）和结核分枝杆菌（rv2719c）为特征的细胞分裂抑制基因具有有限的同源性，但都位于各自基因组的lexA附近。使用这种接近lexA的方法，谷氨酸棒杆菌R divS（cgR1759）被确定为SOS诱导的细胞分裂抑制剂。 DivS的氨基酸序列与YneA和Rv2719c没有同源性。 DNA破坏性丝裂霉素C处理可在野生型细胞中显着诱导divS表达，而在不能诱导SOS应答的DeltarecA突变细胞中则不会。暴露于破坏DNA的丝裂霉素C的野生型谷氨酸棒状杆菌R细胞表现出细长的形态，该形态使用绿色荧光蛋白-FtsZ融合蛋白归因于FtsZ环装配中的缺陷。 FtsZ环组件中有缺陷的细胞随后无法进行隔壁合成。在存在丝裂霉素C的情况下，divS突变细胞没有表现出这种拉长的形态，而过表达divS的细胞则拉长且异常分支。

BACKGROUND & AIMS: :In response to DNA damage from ultraviolet (UV) radiation, bacteria deploy the SOS response in order to limit cell death. This bacterial SOS response is characterized by an increase in the recA gene that transactivates expression of multiple DNA repair genes. The current series of experiments demonstrate that a mammalian organ system (the cochlea) that is not evolutionarily conditioned to UV radiation can elicit SOS responses that are reminiscent of that of bacteria. This mammalian SOS response is characterized by an increase in the p53 gene with activation of multiple DNA repair genes that harbor p53 response elements in their promoters. Furthermore, the experimental results provide support for the notion of a convergent trigger paradox, where independent SOS triggers facilitate disparate physiologic sequelae (loss vs. recovery of function). Therefore, it is proposed that the mammalian SOS response is multifunctional and manipulation of this endogenous response could be exploited in future biomedical interventions.

背景与目标： ：为响应紫外线（UV）辐射对DNA造成的损害，细菌会部署SOS反应以限制细胞死亡。这种细菌的SOS反应的特征是recA基因增加，从而激活多个DNA修复基因的表达。当前的一系列实验表明，未经过紫外线条件进化调节的哺乳动物器官系统（耳蜗）可引起SOS反应，这种反应令人联想到细菌。这种哺乳动物的SOS反应的特征是p53基因的增加，并激活了多个在其启动子中带有p53反应元件的DNA修复基因。此外，实验结果为聚合触发悖论的概念提供了支持，其中独立的SOS触发促进了不同的生理后遗症（功能丧失与功能恢复）。因此，提出哺乳动物的SOS应答是多功能的，并且这种内源应答的操纵可在未来的生物医学干预中加以利用。

BACKGROUND & AIMS: :Molecular mechanisms responsible for the genetic instability of DNA trinucleotide sequences (TRS) account for at least 20 human hereditary disorders. Many aspects of DNA metabolism influence the frequency of length changes in such repeats. Herein, we demonstrate that expression of Escherichia coli SOS repair proteins dramatically decreases the genetic stability of long (CTG/CAG)n tracts contained in plasmids. Furthermore, the growth characteristics of the bacteria are affected by the (CTG/CAG)n tract, with the effect dependent on the length of the TRS. In an E. coli host strain with constitutive expression of the SOS regulon, the frequency of deletions to the repeat is substantially higher than that in a strain with no SOS response. Analyses of the topology of reporter plasmids isolated from the SOS+ and SOS- strains revealed higher levels of negative supercoiling in strains with the constitutively expressed SOS network. Hence, we used strains with mutations in topoisomerases to examine the effect of DNA topology upon the TRS instability. Higher levels of negative DNA supercoiling correlated with increased deletions in long (CTG/CAG)n, (CGG/CCG)n and (GAA/TTC)n. These observations suggest a link between the induction of bacterial SOS repair, changes in DNA topology and the mechanisms leading to genetic instability of repetitive DNA sequences.

背景与目标： ：造成DNA三核苷酸序列（TRS）遗传不稳定性的分子机制至少导致了20种人类遗传性疾病。 DNA代谢的许多方面都会影响此类重复序列长度变化的频率。在本文中，我们证明了大肠杆菌SOS修复蛋白的表达显着降低了质粒中长（CTG / CAG）n片段的遗传稳定性。此外，细菌的生长特性受到（CTG / CAG）n束的影响，其效果取决于TRS的长度。在具有SOS调节子组成型表达的大肠杆菌宿主菌株中，重复序列的缺失频率明显高于无SOS应答的菌株。从SOS和SOS菌株中分离的报告质粒的拓扑分析表明，在具有组成型表达SOS网络的菌株中，负超螺旋水平更高。因此，我们使用在拓扑异构酶中具有突变的菌株来研究DNA拓扑对TRS不稳定性的影响。负DNA超螺旋的较高水平与长（CTG / CAG）n，（CGG / CCG）n和（GAA / TTC）n中缺失的增加相关。这些观察结果表明诱导细菌SOS修复，DNA拓扑结构变化与导致重复DNA序列遗传不稳定的机制之间存在联系。

BACKGROUND & AIMS: RATIONALE AND OBJECTIVES:A previous study demonstrated unexpected protection from satisfaction of search (SOS) effects when observers verbalized the focus of their attention during visual search and interpretation of chest radiographs. We suggested that protection from SOS might have occurred if each observer developed an informal checklist to help generate the verbal descriptions. The objective of this study is to determine whether a formal checklist reduces SOS effects in chest radiology. MATERIALS AND METHODS:Fifty-seven chest radiographs, half of which demonstrated diverse, native abnormalities were read twice by 20 observers, once with and once without the addition of a simulated pulmonary nodule. Area under the receiver operating characteristic (ROC) curve for detecting the native abnormalities was estimated for each observer in each treatment condition using the contaminated binormal ROC model. Radiologists in the current experiment used a checklist during the interpretation, rather than describing their visual search. Results were compared with those of the verbalization study, which used the same set of radiographs. RESULTS:Although no SOS effect was found when the checklist was used, ROC performance was, on average, much poorer with the checklist than when ongoing search was reported verbally (0.68 versus 0.75, F(1, 37) = 17.26, P < .001). CONCLUSIONS:Our results indicate that the recommendation to use a self-prompting checklist to counteract SOS is not warranted. The relative superiority of verbalizing search over using an imposed checklist may be based on the consistency of each of these interventions with the observer's internal strategy for searching radiographs.

背景与目标： 理由和目的：先前的一项研究表明，当观察者在进行胸部X线片的视觉搜索和解释时，将他们的注意力集中在口头上时，其出人意料的保护作用就是免受搜索满意度（SOS）的影响。我们建议，如果每个观察者都制定一份非正式的清单来帮助生成口头描述，则可能会免受SOS的侵害。这项研究的目的是确定正式的检查清单是否能减少胸部放射学中的SOS效应。
材料与方法：57例胸部X线照片中，有20名观察者阅读了两次，其中一半表现出各种自然异常，一次伴有或不伴有模拟性肺结节。使用污染的双正态ROC模型，为每个观察者估计了每种治疗条件下用于检测自然异常的接收器工作特征（ROC）曲线下的面积。当前实验中的放射科医生在解释过程中使用了清单，而不是描述其视觉搜索。将结果与口头化研究的结果进行了比较，后者使用了相同的射线照片。
结果：尽管使用清单时未发现SOS效果，但平均而言，清单中的ROC性能要比口头报告正在进行的搜索时差得多（0.68对0.75，F（1，37）= 17.26，P <。 001）。
结论：我们的结果表明，不建议使用自动提示清单来抵消SOS。言语化搜索相对于使用强制检查表的相对优势可能基于这些干预措施中的每一项与观察者用于搜索射线照片的内部策略的一致性。

BACKGROUND & AIMS: :Induction of the adaptive response by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) caused a decrease in the UV-mediated expression of both recA and sfiA genes but not of the umuDC gene. On the other hand, the adaptive response did not affect the temperature-promoted induction of SOS response in a RecA441 mutant. The inhibitory effect on the UV-triggered expression of the recA and sfiA genes was not dependent on either the alkA gene or the basal level of RecA protein, but rather required the ada gene. Furthermore, an increase in the level of the Ada protein, caused by the runaway plasmid pYN3059 in which the ada gene is regulated by the lac promoter, inhibited UV-mediated recA gene expression even in cells to which the MNNG-adaptive treatment had not been applied. This inhibitory effect of the adaptive pretreatment was not observed either in RecBC- strains or in RecBC mutants lacking exonuclease V-related nuclease activity. However, RecF- mutants showed an adaptive response-mediated decrease in UV-promoted induction of the recA gene.

背景与目标： N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导的适应性反应导致recA和sfiA基因的紫外线介导的表达减少，但umuDC基因的表达却没有减少。另一方面，在RecA441突变体中，适应性应答不影响温度促进的SOS应答诱导。对recA和sfiA基因的紫外线触发表达的抑制作用不依赖于alkA基因或基础水平的RecA蛋白，而是需要ada基因。此外，由失控的质粒pYN3059引起的Ada蛋白水平的增加，其中ada基因受lac启动子调控，甚至在尚未进行MNNG适应性处理的细胞中也抑制了UV介导的recA基因的表达。应用。在RecBC菌株或缺乏核酸外切酶V相关核酸酶活性的RecBC突变体中均未观察到这种自适应预处理的抑制作用。但是，RecF突变体在紫外线促进的recA基因诱导中显示出适应性反应介导的下降。

BACKGROUND & AIMS: :Intrinsically disordered proteins (IDPs) often rely on electrostatic interactions to bind their structured targets. To obtain insight into the mechanism of formation of the electrostatic encounter complex, we investigated the binding of the peptide Sos (PPPVPPRRRR), which serves as a minimal model for an IDP, to the c-Crk N-terminal SH3 domain. Initially, we measured ¹⁵N relaxation rates at two magnetic field strengths and determined the binding shifts for the complex of Sos with wild-type SH3. We have also recorded a 3 μs molecular dynamics (MD) trajectory of this complex using the Amber ff99SB*-ILDN force field. The comparison of the experimental and simulated data shows that MD simulation consistently overestimates the strength of salt bridge interactions at the binding interface. The series of simulations using other advanced force fields also failed to produce any satisfactory results. To address this issue, we have devised an empirical correction to the Amber ff99SB*-ILDN force field whereby the Lennard-Jones equilibrium distance for the nitrogen-oxygen pair across the Arg-to-Asp and Arg-to-Glu salt bridges has been increased by 3%. Implementing this correction resulted in a good agreement between the simulations and the experiment. Adjusting the strength of salt bridge interactions removed a certain amount of strain contained in the original MD model, thus improving the binding of the hydrophobic N-terminal portion of the peptide. The arginine-rich C-terminal portion of the peptide, freed from the effect of the overstabilized salt bridges, was found to interconvert more rapidly between its multiple conformational states. The modified MD protocol has also been successfully used to simulate the entire binding process. In doing so, the peptide was initially placed high above the protein surface. It then arrived at the correct bound pose within ∼2 Å of the crystallographic coordinates. This simulation allowed us to analyze the details of the dynamic binding intermediate, i.e., the electrostatic encounter complex. However, an experimental characterization of this transient, weakly populated state remains out of reach. To overcome this problem, we designed the double mutant of c-Crk N-SH3 in which mutations Y186L and W169F abrogate tight Sos binding and shift the equilibrium toward the intermediate state resembling the electrostatic encounter complex. The results of the combined NMR and MD study of this engineered system will be reported in the next part of this paper.

背景与目标： ：固有的无序蛋白（IDP）通常依靠静电相互作用来结合其结构化靶标。为了深入了解静电相遇复合物的形成机理，我们研究了肽Sos（PPPVPPRRRR）作为IDP的最小模型，与c-Crk N末端SH3结构域的结合。最初，我们在两个磁场强度下测量了1 N的弛豫率，并确定了Sos与野生型SH3的复合物的结合位移。我们还使用琥珀色ff99SB * -ILDN力场记录了该复合物的3μs分子动力学（MD）轨迹。实验数据和模拟数据的比较表明，MD模拟始终高估了结合界面上盐桥相互作用的强度。使用其他先进的力场进行的一系列模拟也未能产生任何令人满意的结果。为解决此问题，我们对Affff ff99SB * -ILDN琥珀色力场进行了经验校正，据此得出了横跨Arg-to-Asp和Arg-to-Glu盐桥的氮氧对的Lennard-Jones平衡距离增加了3％。实施此校正可在仿真和实验之间取得良好的一致性。调节盐桥相互作用的强度去除了原始MD模型中包含的一定量的应变，从而改善了肽的疏水性N-末端部分的结合。发现该肽的富含精氨酸的C-末端部分不受过度稳定的盐桥的影响，可以在其多种构象状态之间更快速地相互转化。修改后的MD协议也已成功用于模拟整个绑定过程。为此，首先将肽放置在蛋白质表面上方的较高位置。然后，它到达晶体学坐标约2Å以内的正确束缚姿势。这种模拟使我们能够分析动态结合中间体的细节，即静电相遇复合物。但是，这种瞬态，人口稀少状态的实验表征仍然遥不可及。为了克服这个问题，我们设计了c-Crk N-SH3的双突变体，其中突变Y186L和W169F消除了紧密的Sos结合，并使平衡向类似于静电相遇复合物的中间态移动。此工程系统的NMR和MD结合研究的结果将在本文的下一部分中报告。

BACKGROUND & AIMS: :The effectiveness of heavy ions in inducing the SOS response in E. coli cells has been measured by means of the SOS-chromotest. The SOS induction potency of ionizing radiation increases with increasing LET, to 40-60 keV/microns, reaches a maximum and then decreases at greater LET values. We conclude that the SOS-inducing damages in the case of ionizing radiation could be DNA injuries of a 'complex' type, e.g., DNA double-strand breaks or some kind of heavily damaged single-strand lesions.

背景与目标： ：已经通过SOS-chromotest测量了重离子在大肠杆菌细胞中诱导SOS应答的有效性。电离辐射的SOS诱导能力随着LET的增加而增加，达到40-60 keV /微米，达到最大值，然后在更大的LET值时降低。我们得出的结论是，在电离辐射的情况下，诱导SOS的损害可能是``复杂''类型的DNA损伤，例如DNA双链断裂或某种严重受损的单链损伤。

BACKGROUND & AIMS: :The genotoxic activity of 11 mycotoxins was investigated in Escherichia coli K 12. The induction of the SOS function sfi A whose level of expression is monitored by means of a sfi A::lac Z operon fusion was assayed by measuring the beta-galactosidase activity in the PQ 37 strain. Most of these fungal metabolites did not induce SOS response in this bacterial test. Only aflatoxicol, a reduced metabolite of aflatoxin B1 was well detected as an SOS inducer if metabolic activation was performed. Patulin, penicillic acid and viomellein are only weak inducing agents. The other fungal compounds tested failed to demonstrate a positive SOS inducing activity. Relationship between SOS chromotest, mutagenicity to Salmonella typhimurium and in vivo carcinogenicity was discussed.

背景与目标： ：在大肠杆菌K 12中研究了11种霉菌毒素的遗传毒性活性。通过测量β-半乳糖苷酶活性来测定SOS功能sfi A的诱导，其表达水平通过sfi A :: lac Z操纵子融合体进行监测在PQ 37株中。这些真菌代谢物中的大多数在此细菌测试中均未诱导SOS反应。如果进行了代谢激活，则只有黄曲霉酚（一种降低的黄曲霉毒素B1代谢产物）可以作为SOS诱导剂被很好地检测到。棒曲霉素，青霉酸和堇青素仅是弱诱导剂。测试的其他真菌化合物未能显示出积极的SOS诱导活性。讨论了SOS显色性，对鼠伤寒沙门氏菌的致突变性与体内致癌性之间的关系。

BACKGROUND & AIMS: :The SOS Chromotest on Escherichia coli strain PQ37 was used to detect DNA damage induced by 16 chemical compounds and urine samples from smokers and a non-smoking psoriatic patient treated with mineral coal tar. The results confirmed the strong SOS inducing activity of 2-aminoanthracene and benzo[a]pyrene with metabolic activation and N-methyl-N'-nitro-N-nitrosoguanidine, mitomycin C and 4-nitroquinoline-N-oxide without metabolic activation. A weaker response in the absence of microsomal enzymes was observed with hydroxyurea (only at high doses) and the soluble Cr(VI) compounds potassium chromate and potassium dichromate. No effect was observed with ampicillin, cadmium chloride, cyclophosphamide, griseofulvin, the insoluble Cr(VI) compound lead chromate, the soluble Cr(III) compounds chromium nitrate, chromium chloride, chromium potassium sulphate, and the chelating agent sodium nitrilotriacetate. Among the Cr(III) compounds only chromium acetate produced a low but significant increase of SOS inducing activity. Solubilization by nitrilotriacetate of genotoxic Cr(VI) from insoluble lead chromate was observed, whereas no interaction occurred between nitrilotriacetate and the soluble Cr(VI) and Cr(III) compounds. Using urinary XAD-2 extracts, we found the SOS Chromotest poorly sensitive to the mutagens present in urine from tobacco smokers which, on the other hand, were detected by the gene mutation assay in Salmonella typhimurium (Ames test). A urine sample obtained from a psoriatic patient, therapeutically treated with mineral coal tar, had a significant SOS inducing activity with and even without metabolic activation, whereas in the Ames test it was active only in the presence of metabolic activation.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： ：使用SOS Chromotest对大肠杆菌PQ37菌株进行检测，以检测由16种化合物和吸烟者以及一名接受矿物煤焦油治疗的非吸烟性银屑病患者的尿液样品引起的DNA损伤。该结果证实了具有2-甲基蒽和苯并[a] py具有代谢活化和没有代谢活化的N-甲基-N'-硝基-N-亚硝基胍，丝裂霉素C和4-硝基喹啉-N-氧化物的强SOS诱导活性。使用羟基脲（仅在高剂量时）和可溶性Cr（VI）化合物铬酸钾和重铬酸钾观察到在不存在微粒体酶的情况下响应较弱。氨苄青霉素，氯化镉，环磷酰胺，灰黄霉素，不溶性Cr（VI）化合物铬酸铅，可溶性Cr（III）化合物硝酸铬，氯化铬，硫酸铬钾和螯合剂次氮基三乙酸钠未见效果。在Cr（III）化合物中，只有乙酸铬产生的SOS诱导活性低但显着增加。观察到次氮基三乙酸盐从不溶的铬酸铅中溶解了具有遗传毒性的Cr（VI），而次氮基三乙酸盐与可溶性Cr（VI）和Cr（III）化合物之间未发生相互作用。使用尿液XAD-2提取物，我们发现SOS Chromotest对吸烟者尿液中存在的诱变剂不敏感，而另一方面，通过鼠伤寒沙门氏菌的基因突变检测（Ames试验）检测到了。从银屑病患者接受矿物煤焦油治疗的尿液样品在有或没有代谢活化的情况下均具有显着的SOS诱导活性，而在Ames试验中，它仅在存在代谢活化的情况下才具有活性。（摘要摘录于250字）

BACKGROUND & AIMS: :The SOS response is readily triggered by replication fork stalling caused by DNA damage or a dysfunctional replicative apparatus in Escherichia coli cells. E. coli dinB encodes DinB DNA polymerase and its expression is upregulated during the SOS response. DinB catalyzes translesion DNA synthesis in place of a replicative DNA polymerase III that is stalled at a DNA lesion. We showed previously that DNA replication was suppressed without exogenous DNA damage in cells overproducing DinB. In this report, we confirm that this was due to a dose-dependent inhibition of ongoing replication forks by DinB. Interestingly, the DinB-overproducing cells did not significantly induce the SOS response even though DNA replication was perturbed. RecA protein is activated by forming a nucleoprotein filament with single-stranded DNA, which leads to the onset of the SOS response. In the DinB-overproducing cells, RecA was not activated to induce the SOS response. However, the SOS response was observed after heat-inducible activation in strain recA441 (encoding a temperature-sensitive RecA) and after replication blockage in strain dnaE486 (encoding a temperature-sensitive catalytic subunit of the replicative DNA polymerase III) at a non-permissive temperature when DinB was overproduced in these cells. Furthermore, since catalytically inactive DinB could avoid the SOS response to a DinB-promoted fork block, it is unlikely that overproduced DinB takes control of primer extension and thus limits single-stranded DNA. These observations suggest that DinB possesses a feature that suppresses DNA replication but does not abolish the cell's capacity to induce the SOS response. We conclude that DinB impedes replication fork progression in a way that does not activate RecA, in contrast to obstructive DNA lesions and dysfunctional replication machinery.

背景与目标： ：SOS响应很容易因DNA损伤或大肠杆菌细胞复制装置功能异常而引起的复制叉停转而触发。大肠杆菌dinB编码DinB DNA聚合酶，并且在SOS反应期间其表达上调。 DinB可以催化停滞在DNA病变处的复制型DNA聚合酶III，从而催化跨病变的DNA合成。我们以前表明，在过量生产DinB的细胞中，DNA复制被抑制而没有外源DNA损伤。在此报告中，我们确认这是由于DinB对正在进行的复制叉的剂量依赖性抑制。有趣的是，即使DNA复制受到干扰，DinB过量产生细胞也不会显着诱导SOS反应。 RecA蛋白通过形成具有单链DNA的核蛋白丝而被激活，从而导致SOS反应的发生。在过量产生DinB的细胞中，RecA没有被激活以诱导SOS反应。但是，在菌株recA441中的热诱导激活（编码温度敏感的RecA）之后和在菌株dnaE486中的复制受阻（编码复制性DNA聚合酶III的温度敏感催化亚基）非允许的情况下，观察到了SOS反应。 DinB在这些细胞中过量产生时的温度。此外，由于具有催化活性的DinB可以避免SOS对DinB促进的叉叉反应的应答，因此过量生产的DinB不太可能控制引物延伸并因此限制了单链DNA。这些观察结果表明，DinB具有抑制DNA复制但不会消除细胞诱导SOS反应的能力的功能。我们得出的结论是，与阻塞性DNA损伤和功能障碍的复制机制相反，DinB以不激活RecA的方式阻碍了复制叉的发展。

BACKGROUND & AIMS: :Four nitroarenes were tested in two standard genotoxicity assay systems using three well-known bacterial tester strains. The results were as follows: 4-nitroquinoline l-oxide (4NQO) was positive in Quillardet and Hofnung's SOS chromotest using Escherichia coli strain PQ37 both in the presence and absence of microsomal (S9) supplements and in the Salmonella typhimurium umu tester strains NM2009 and NM3009, which express high levels of O-acetyltransferase (O-AT) and O-AT plus nitroreductase (NR) respectively. m-Nitrocinnamic acid (m-NCA) was weakly positive in strains NM2009 and NM3009, but negative in the SOS chromotest; m-dinitrobenzene (m-DNB) was weakly positive in strain NM2009, intermediate positive in strain NM3009, but negative in the SOS chromotest; 2,4-dinitrotoluene (2,4-DNT) was weakly positive in strain NM3009, but negative in strain NM2009 and in the SOS chromotest. However it still showed a dose-response relationship in strain NM2009. In view of these results, it is suggested that investigators planning to screen miscellaneous nitroarenes for their genotoxicity in the future should consider taking advantage of the increased sensitivity which is conferred on S. typhimurium strains NM2009 and NM3009 by virtue of their capacity to overexpress O-AT or O-AT and NR.

背景与目标： 在四个标准的遗传毒性测定系统中，使用三种著名的细菌测试菌株对四个硝基芳烃进行了测试。结果如下：在存在和不存在微粒体（S9）补充剂和鼠伤寒沙门氏菌UM2009测试株中，使用大肠杆菌PQ37菌株在Quillardet和Hofnung的SOS色度测试中，4-硝基喹啉L-氧化物（4NQO）呈阳性。 NM3009，分别表达高水平的O-乙酰基转移酶（O-AT）和O-AT加硝基还原酶（NR）。间硝基肉桂酸（m-NCA）在NM2009和NM3009菌株中呈弱阳性，但在SOS色度测试中呈阴性。间二硝基苯（m-DNB）在NM2009菌株中呈弱阳性，在NM3009菌株中呈中等阳性，但在SOS色度测试中呈阴性。 2,4-二硝基甲苯（2,4-DNT）在NM3009菌株中呈弱阳性，而在NM2009菌株和SOS色度试验中呈阴性。然而，它仍然显示出菌株NM2009中的剂量反应关系。鉴于这些结果，建议研究人员计划将来筛选其他硝基芳烃的遗传毒性，应考虑利用鼠伤寒沙门氏菌菌株NM2009和NM3009的敏感性增强，因为它们具有过表达O-的能力。 AT或O-AT和NR。

BACKGROUND & AIMS: :The 6C RNA family is a class of small RNAs highly conserved in Actinobacteria, including the genera Mycobacterium, Streptomyces and Corynebacterium whose physiological function has not yet been elucidated. We found that strong transcription of the cgb_03605 gene, which encodes 6C RNA in C. glutamicum, was driven by the SigA- and SigB-dependent promoter Pcgb_03605. 6C RNA was detected at high level during exponential growth phase (180 to 240 molcules per cell) which even increased at the entry of the stationary phase. 6C RNA level did not decrease within 240 min after transcription had been stopped with rifampicin, which suggests high 6C RNA stability. The expression of cgb_03605 further increased approximately twofold in the presence of DNA-damaging mitomycin C (MMC) and nearly threefold in the absence of LexA. Deletion of the 6C RNA gene cgb_03605 resulted in a higher sensitivity of C. glutamicum toward MMC and UV radiation. These results indicate that 6C RNA is involved in the DNA damage response. Both 6C RNA level-dependent pausing of cell growth and branched cell morphology in response to MMC suggest that 6C RNA may also be involved in a control of cell division.

背景与目标： ：6C RNA家族是放线菌中高度保守的一类小RNA，包括尚未阐明其生理功能的分枝杆菌属，链霉菌属和棒状杆菌属。我们发现，由SigA和SigB依赖性启动子Pcgb_03605驱动cgb_03605基因的强转录，该基因在谷氨酸棒杆菌中编码6C RNA。在指数生长期（每个细胞180到240分子），高水平检测到6C RNA，甚至在固定相进入时也增加。用利福平终止转录后240分钟内6C RNA水平没有降低，这表明6C RNA的稳定性很高。在存在破坏DNA的丝裂霉素C（MMC）的情况下，cgb_03605的表达进一步增加了约两倍，而在不存在LexA的情况下，其表达则增加了近三倍。 6C RNA基因cgb_03605的删除导致谷氨酸棒杆菌对MMC和UV辐射的敏感性更高。这些结果表明6C RNA参与了DNA损伤反应。响应MMC的6C RNA水平依赖性细胞生长暂停和分支细胞形态均表明6C RNA也可能参与细胞分裂的控制。

BACKGROUND & AIMS: To examine the concordance of two microbial genotoxicity short-term assays, 330 experimental results for the SOS chromotest using tester strain Escherichia coli PQ37 were compared with the results of the Salmonella/mammalian microsome mutagenicity assay with Salmonella typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and/or TA1538. With respect to qualitative features, the concordance between SOS chromotest and Salmonella mutagenicity test results was 86.4% (sensitivity, 78.6%; specificity, 100%; chi 2 = 188.6). None of the non-mutagens (N = 120) were able to induce the SOS system. Additionally, 45 of the 210 S.typhimurium mutagens (21.5%) did not induce the SOS repair system. On closer examination, the majority of these 45 compounds (84%) were mutagens with activities between 0.001 and 10 rev/nmol. Even though the experimental protocols of both systems were not standardized, the correlation coefficient for the experimental results of the two test systems was 0.7 for the 330 chemicals. Except for aliphatic epoxides (r = 0.47), the mutagenicity/SOS induction correlations for congeneric data sets (polycyclic aromatic hydrocarbons, nitroarenes, nitroarenofurans, mycotins) were even better (r = 0.72-0.95). Additionally, computer automated structure evaluation (CASE) analyses of the nature of the structural determinants associated with each endpoint indicate extensive homologies. The data can be taken to indicate that the two phenomena reflect common mechanisms of action.

背景与目标： 为了检验两种微生物遗传毒性短期测定的一致性，将330例使用测试菌株Escherichia coli PQ37进行SOS色度测试的实验结果与采用鼠伤寒沙门氏菌TA97，TA98，TA100，TA102， TA104，TA1535，TA1537和/或TA1538。就定性特征而言，SOS色度测试与沙门氏菌诱变测试结果之间的一致性为86.4％（敏感性为78.6％；特异性为100％； chi 2 = 188.6）。所有非突变体（N = 120）均无法诱导SOS系统。此外，210个鼠伤寒沙门氏菌中有45个（21.5％）没有诱导SOS修复系统。经仔细检查，这45种化合物中的大多数（84％）是诱变剂，其活性在0.001和10 rev / nmol之间。即使两个系统的实验方案均未标准化，但对于330种化学品，两个测试系统的实验结果的相关系数均为0.7。除脂族环氧化物（r = 0.47）外，同类数据集（多环芳烃，硝基芳烃，硝基芳呋喃，霉菌毒素）的诱变性/ SOS诱导相关性甚至更好（r = 0.72-0.95）。此外，与每个端点关联的结构决定因素的性质的计算机自动结构评估（CASE）分析表明，存在广泛的同源性。可以得出的数据表明这两种现象反映了共同的作用机理。

BACKGROUND & AIMS: :Quinolone antibacterial drugs such as nalidixic acid target DNA gyrase in Escherichia coli. These inhibitors bind to and stabilize a normally transient covalent protein-DNA intermediate in the gyrase reaction cycle, referred to as the cleavage complex. Stabilization of the cleavage complex is necessary but not sufficient for cell killing--cytotoxicity apparently results from the conversion of cleavage complexes into overt DNA breaks by an as-yet-unknown mechanism(s). Quinolone treatment induces the bacterial SOS response in a RecBC-dependent manner, arguing that cleavage complexes are somehow converted into double-stranded breaks. However, the only proteins known to be required for SOS induction by nalidixic acid are RecA and RecBC. In hopes of identifying additional proteins involved in the cytotoxic response to nalidixic acid, we screened for E. coli mutants specifically deficient in SOS induction upon nalidixic acid treatment by using a dinD::lacZ reporter construct. From a collection of SOS partially constitutive mutants with disruptions of 47 different genes, we found that dnaQ insertion mutants are specifically deficient in the SOS response to nalidixic acid. dnaQ encodes DNA polymerase III epsilon subunit, the proofreading subunit of the replicative polymerase. The deficient response to nalidixic acid was rescued by the presence of the wild-type dnaQ gene, confirming involvement of the epsilon subunit. To further characterize the SOS deficiency of dnaQ mutants, we analyzed the expression of several additional SOS genes in response to nalidixic acid using real-time PCR. A subset of SOS genes lost their response to nalidixic acid in the dnaQ mutant strain, while two tested SOS genes (recA and recN) continued to exhibit induction. These results argue that the replication complex plays a role in modulating the SOS response to nalidixic acid and that the response is more complex than a simple on/off switch.

背景与目标： ：喹诺酮类抗菌药物，例如萘啶酸可靶向大肠杆菌中的DNA促旋酶。这些抑制剂在促旋酶反应周期中结合并稳定通常短暂的共价蛋白-DNA中间体，称为裂解复合物。裂解复合物的稳定对于杀死细胞是必要的，但还不足以使细胞毒性-细胞毒性显然是由于裂解复合物通过迄今未知的机制转化为明显的DNA断裂所致。喹诺酮治疗以RecBC依赖的方式诱导细菌SOS反应，认为裂解复合物以某种方式转化为双链断裂。但是，已知萘啶酸诱导SOS所需的唯一蛋白质是RecA和RecBC。为了希望鉴定涉及对萘啶酸的细胞毒性反应的其他蛋白质，我们使用dinD :: lacZ报告基因构建体筛选了在萘啶酸处理后特异缺乏SOS诱导作用的大肠杆菌突变体。从具有47个不同基因破坏的SOS部分组成性突变体的集合中，我们发现dnaQ插入突变体在SOS对萘啶酸的反应中特别缺乏。 dnaQ编码DNA聚合酶IIIε亚基，即复制性聚合酶的校对亚基。野生型dnaQ基因的存在挽救了对萘啶酸的不足反应，证实了ε亚基的参与。为了进一步表征dnaQ突变体的SOS缺陷，我们使用实时PCR分析了响应于萘啶酸的一些其他SOS基因的表达。 SOS基因的一个子集在dnaQ突变菌株中失去了对萘啶酸的反应，而两个测试的SOS基因（recA和recN）继续表现出诱导作用。这些结果表明复制复合物在调节SOS对萘啶酸的反应中起作用，并且该反应比简单的开/关开关更复杂。