NDLI: SOS mutator activity: Unequal mutagenesis on leading and lagging strands

Content Provider	PubMed Central
Author	Magdalena, Maliszewska-tkaczyk Jonczyk, Piotr Bialoskorska, Malgorzata Schaaper, Roel M. Fijalkowska, Iwona J.
Copyright Year	2000
Abstract	A major pathway of mutagenesis in Escherichia coli is mediated by the inducible SOS response. Current models of SOS mutagenesis invoke the interaction of RecA and UmuD′2C proteins with a stalled DNA replication complex at sites of DNA lesions or poorly extendable terminal mismatches, resulting in an (error-prone) continuation of DNA synthesis. The precise mechanisms of SOS-mediated lesion bypass or mismatch extension are not known. Here, we have studied mutagenesis on the E. coli chromosome in recA730 strains. In recA730 strains, the SOS system is expressed constitutively, resulting in a spontaneous mutator effect (SOS mutator) because of reduced replication fidelity. We investigated whether during SOS mutator activity replication fidelity might be altered differentially in the leading and lagging strand of replication. Pairs of recA730 strains were constructed differing in the orientation of the lac operon relative to the origin of replication. The strains were also mismatch-repair defective (mutL) to facilitate scoring of replication errors. Within each pair, a given lac sequence is replicated by the leading-strand machinery in one orientation and by the lagging-strand machinery in the other orientation. Measurements of defined lac mutant frequencies in such pairs revealed large differences between the two orientations. Furthermore, in all cases, the frequency bias was the opposite of that seen in normal cells. We suggest that, for the lacZ target used in this study, SOS mutator activity operates with very different efficiency in the two strands. Specifically, the lagging strand of replication appears most susceptible to the SOS mutator effect.
Related Links	http://dx.doi.org/10.1073/pnas.220424697
Ending Page	12683
Page Count	6
Starting Page	12678
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	23
Volume Number	97
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2000-11-07
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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