Stationary-Phase Mutagenesis in Stressed Bacillus subtilis Cells Operates by Mfd-Dependent Mutagenic Pathways.
Stationary-Phase Mutagenesis in Stressed Bacillus subtilis Cells Operates by Mfd-Dependent Mutagenic Pathways.
复制标题
压力性枯草芽孢杆菌细胞中的固定相诱变通过MFD依赖性诱变途径运行。
DOI：
10.3390/genes7070033
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发表时间：
2016-07-05
期刊：
影响因子：
3.5
通讯作者：
Robleto EA
中科院分区：
文献类型：
--
作者：
Gómez-Marroquín M;Martin HA;Pepper A;Girard ME;Kidman AA;Vallin C;Yasbin RE;Pedraza-Reyes M;Robleto EA
在枯草芽孢杆菌的复制受限细胞中，Mfd在高度转录的区域是致突变的，即使在没有大体积DNA损伤的情况下。然而，通过Mfd导致突变增加的机制目前仍然未知。在这里，我们报告说，Mfd可能会促进诱变营养强调B。枯草杆菌细胞通过协调由UvrA，MutY和PolI介导的易错修复事件。使用点突变的基因赋予亮氨酸营养缺陷型作为遗传标记，它被发现，UvrA的情况下，减少了Leu+回复突变体和第二突变mfd进一步减少诱变。此外，与亲本菌株相比，mfd和polA突变体呈现低但相似的回复频率。这些结果表明，Mfd促进需要NER途径和PolI参与的致突变事件。值得注意的是，发现这种Mfd依赖性诱变途径对MutY具有上位性;然而，尽管MutY依赖性Leu+回复需要Mfd，但这些蛋白质之间的直接相互作用并不明显。总之，我们的结果支持Mfd促进饥饿B中突变的概念。通过协调已知的和以前未知的Mfd相关修复途径，在枯草杆菌细胞中表达。这些诱变过程使遗传多样性的产生偏向于基因组中高度转录的区域。
In replication-limited cells of Bacillus subtilis, Mfd is mutagenic at highly transcribed regions, even in the absence of bulky DNA lesions. However, the mechanism leading to increased mutagenesis through Mfd remains currently unknown. Here, we report that Mfd may promote mutagenesis in nutritionally stressed B. subtilis cells by coordinating error-prone repair events mediated by UvrA, MutY and PolI. Using a point-mutated gene conferring leucine auxotrophy as a genetic marker, it was found that the absence of UvrA reduced the Leu+ revertants and that a second mutation in mfd reduced mutagenesis further. Moreover, the mfd and polA mutants presented low but similar reversion frequencies compared to the parental strain. These results suggest that Mfd promotes mutagenic events that required the participation of NER pathway and PolI. Remarkably, this Mfd-dependent mutagenic pathway was found to be epistatic onto MutY; however, whereas the MutY-dependent Leu+ reversions required Mfd, a direct interaction between these proteins was not apparent. In summary, our results support the concept that Mfd promotes mutagenesis in starved B. subtilis cells by coordinating both known and previously unknown Mfd-associated repair pathways. These mutagenic processes bias the production of genetic diversity towards highly transcribed regions in the genome.