Greater Susceptibility to Mutations in Lagging Strand of DNA Replication in
            <i>Escherichia coli</i>
            than in Leading Strand

Veaute, Xavier; Fuchs, Robert P. P.

doi:10.1126/science.8342022

Cited by 108 publications

(79 citation statements)

References 15 publications

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“…Many authors have found that error rates are higher on the lagging strand (e.g. Trinh and Sinden 1991;BasicZaninovic et al 1992;Veaute and Fuchs 1993;Roberts et al 1994;Iwaki et al 1996;Thomas et al 1996). However, Fijałkowska et al (1998), measuring the mutation rate in the lactose operon incorporated into the Escherichia coli chromosome in two opposite directions, have found that mutation rate in the gene inserted in the direction of the leading strand is higher.…”

Section: Chargaff Rules [A] ‫ס‬ [T] and [G] ‫ס‬ [C]mentioning

confidence: 99%

Evolution Rates of Genes on Leading and Lagging DNA Strands

et al. 2001

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Abstract.One of the main causes of bacterial chromosome asymmetry is replication-associated mutational pressure. Different rates of nucleotide substitution accumulation on leading and lagging strands implicate qualitative and quantitative differences in the accumulation of mutations in protein coding sequences lying on different DNA strands. We show that the divergence rate of orthologs situated on leading strands is lower than the divergence rate of those situated on lagging strands. The ratio of the mutation accumulation rate for sequences lying on lagging strands to that of sequences lying on leading strands is rather stable and time-independent. The divergence rate of sequences which changed their positions, with respect to the direction of replication fork movement, is not stable-sequences which have recently changed their positions are the most prone to mutation accumulation. This effect may influence estimations of evolutionary distances between species and the topology of phylogenetic trees.

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Section: Chargaff Rules [A] ‫ס‬ [T] and [G] ‫ס‬ [C]mentioning

confidence: 99%

Evolution Rates of Genes on Leading and Lagging DNA Strands

et al. 2001

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“…In addition, in E. coli, it has been observed that the manner in which a given DNA lesion is dealt with depends on the direction of replication [20]. When a plasmid containing a defined DNA lesion was transformed into E. coli cells, the resulting mutation frequency was distinctly different depending on whether the lesion was located on the leading-strand template versus the lagging-strand template [20].…”

Section: Introductionmentioning

confidence: 99%

Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication

et al. 2007

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A high level of transcription has been associated with elevated spontaneous mutation and recombination rates in eukaryotic organisms. To determine whether the transcription level is directly correlated with the degree of genomic instability, we have developed a tetracycline-regulated LYS2 reporter system to modulate the transcription level over a broad range in Saccharomyces cerevisiae. We find that spontaneous mutation rate is directly proportional to the transcription level, suggesting that movement of RNA polymerase through the target initiates a mutagenic process(es). Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): 1) transcription impairs replication fork progression in a directional manner and 2) DNA lesions accumulate under high-transcription conditions. The effect of replication fork progression was probed by comparing the mutational rates and spectra in yeast strains with the reporter gene placed in two different orientations near a well-characterized replication origin. The effect of endogenous DNA damage accumulation was investigated by studying TAM in strains defective in nucleotide excision repair or in lesion bypass by the translesion polymerase Polζ. Our results suggest that both replication orientation and endogenous lesion accumulation play significant roles in TAM, particularly in terms of mutation spectra.

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“…The question of differential replication fidelity within the two strands is a subject of current interest (21)(22)(23)(24)(25)(26)(27). A strand preference of the SOS process, if observed, would be of mechanistic importance.…”

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confidence: 99%

SOS mutator activity: Unequal mutagenesis on leading and lagging strands

Maliszewska-Tkaczyk

Jonczyk

Bialoskorska

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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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 laggingstrand 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.

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Greater Susceptibility to Mutations in Lagging Strand of DNA Replication in Escherichia coli than in Leading Strand

Cited by 108 publications

References 15 publications

Evolution Rates of Genes on Leading and Lagging DNA Strands

Evolution Rates of Genes on Leading and Lagging DNA Strands

Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication

SOS mutator activity: Unequal mutagenesis on leading and lagging strands

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