Characterization of the global transcriptional responses to different types of DNA damage and disruption of replication in Bacillus subtilis
Characterization of the global transcriptional responses to different types of DNA damage and disruption of replication in Bacillus subtilis
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DOI：
10.1128/jb.00342-06
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发表时间：
2006-08-01
影响因子：
3.2
通讯作者：
Grossman, Alan D.
中科院分区：
文献类型：
--
作者：
Goranov, Alexi I.;Kuester-Schoeck, Elke;Grossman, Alan D.
DNA损伤和DNA复制中的扰动可以诱导全局转录反应，这些反应可以帮助生物体修复损伤并存活。已知RecA通过使阻遏物莱克萨和噬菌体阻遏物失活来介导几种细菌物种中对DNA损伤的转录应答。为了深入了解枯草芽孢杆菌如何对各种类型的DNA损伤作出反应，我们通过使用DNA微阵列测量了DNA损伤和复制中的扰动对mRNA水平的影响。我们干扰复制直接与对羟基苯偶氮尿嘧啶（HPUra），DNA聚合酶的抑制剂，或间接与DNA损伤试剂丝裂霉素C（MMC）和紫外线照射。我们的研究结果表明，HPURA，MMC和UV的转录反应只有部分重叠。recA是所有测试条件下的主要转录调节因子，并且莱克萨似乎直接抑制26个操纵子中的63个基因的表达，包括先前鉴定为莱克萨靶的18个操纵子。MMC和HPUra处理引起整合和接合元件（ICEBs 1）和常驻原噬菌体（PBSX和SP β）的诱导，这影响了许多宿主基因的表达。与以前的结果一致，这些移动的元素的诱导需要recA。噬菌体的诱导似乎需要灭活莱克萨。未修复的紫外线损伤和MMC治疗也影响了一些由DnaA控制的基因的表达。此外，MMC治疗引起了近端基因剂量的增加。我们的研究结果表明，不同类型的DNA损伤有不同的影响复制和全球转录谱。
DNA damage and perturbations in DNA replication can induce global transcriptional responses that can help organisms repair the damage and survive. RecA is known to mediate transcriptional responses to DNA damage in several bacterial species by inactivating the repressor LexA and phage repressors. To gain insight into how Bacillus subtilis responds to various types of DNA damage, we measured the effects of DNA damage and perturbations in replication on mRNA levels by using DNA microarrays. We perturbed replication either directly with p-hydroxyphenylazo-uracil (HPUra), an inhibitor of DNA polymerase, or indirectly with the DNA-damaging reagents mitomycin C (MMC) and UV irradiation. Our results indicate that the transcriptional responses to HPUra, MMC, and UV are only partially overlapping. recA is the major transcriptional regulator under all of the tested conditions, and LexA appears to directly repress the expression of 63 genes in 26 operons, including the 18 operons previously identified as LexA targets. MMC and HPUra treatments caused induction of an integrative and conjugative element (ICEBs1) and resident prophages (PBSX and SP beta), which affected the expression of many host genes. Consistent with previous results, the induction of these mobile elements required recA. Induction of the phage appeared to require inactivation of LexA. Unrepaired UV damage and treatment with MMC also affected the expression of some of the genes that are controlled by DnaA. Furthermore, MMC treatment caused an increase in origin-proximal gene dosage. Our results indicate that different types of DNA damage have different effects on replication and on the global transcriptional profile.