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Genes 2016, 7(7), 33;

Stationary-Phase Mutagenesis in Stressed Bacillus subtilis Cells Operates by Mfd-Dependent Mutagenic Pathways

Department of Biology, Division of Natural and Exact Sciences, University of Guanajuato, Noria Alta S/N, Noria Alta, Guanajuato 36050, México
School of Life Sciences, University of Nevada, 4505 Maryland Parkway, Las Vegas, NV 89154, USA
College of Arts and Sciences, University of Missouri-St Louis, 303 Lucas Hall, One University Boulevard, St. Louis, MO 63121, USA
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Richard T. Pomerantz
Received: 30 April 2016 / Revised: 22 June 2016 / Accepted: 24 June 2016 / Published: 5 July 2016
(This article belongs to the Special Issue Replication and Transcription Associated DNA Repair)
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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. View Full-Text
Keywords: transcription-mediated mutagenesis; Mfd; NER; MutY; PolI transcription-mediated mutagenesis; Mfd; NER; MutY; PolI

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Gómez-Marroquín, M.; Martin, H.A.; Pepper, A.; Girard, M.E.; Kidman, A.A.; Vallin, C.; Yasbin, R.E.; Pedraza-Reyes, M.; Robleto, E.A. Stationary-Phase Mutagenesis in Stressed Bacillus subtilis Cells Operates by Mfd-Dependent Mutagenic Pathways. Genes 2016, 7, 33.

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