Directionality of DNA replication fork movement strongly affects the generation of spontaneous mutations in Escherichia coli

Yoshiyama, Kaoru; Higuchi, Kiyoshi; Matsumura, Hironobu; Maki, Hisaji

doi:10.1006/jmbi.2001.4557

Cited by 46 publications

(63 citation statements)

References 18 publications

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“…Testing bidirectionality of transfer: Results obtained in E. coli suggest a bias in the preferred direction of mutagenic templating between the two potential donor/recipient elements of a QP (Trinh and Sinden 1991;Rosche et al 1997;Viswanathan et al 2000;Yoshiyama et al 2001). When the direction of DNA synthesis is fixed, as it is in E. coli, such polarity might reflect an underlying difference in the vulnerabilities of the leading and lagging strands or perhaps an association with the direction of transcription (Yoshiyama and Maki 2003).…”

Section: Resultsmentioning

confidence: 99%

Templated Mutagenesis in Bacteriophage T4 Involving Imperfect Direct or Indirect Sequence Repeats

Schultz

Drake

2008

Genetics

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Some mutations arise in association with a potential sequence donor that consists of an imperfect direct or reverse repeat. Many such mutations are complex; that is, they consist of multiple close sequence changes. Current models posit that the primer terminus of a replicating DNA molecule dissociates, reanneals with an ectopic template, extends briefly, and then returns to the cognate template, bringing with it a locally different sequence; alternatively, a hairpin structure may form the mutational intermediate when processed by mismatch repair. This process resembles replication repair, in which primer extension is blocked by a lesion in the template; in this case, the ectopic template is the other daughter strand, and the result is errorfree bypass of the lesion. We previously showed that mutations that impair replication repair can enhance templated mutagenesis. We show here that the intensity of templated mutation can be exquisitely sensitive to its local sequence, that the donor and recipient arms of an imperfect inverse repeat can exchange roles, and that double mutants carrying two alleles, each affecting both templated mutagenesis and replication repair, can have unexpected phenotypes. We also record an instance in which the mutation rates at two particular sites change concordantly with a distant sequence change, but in a manner that appears unrelated to templated mutagenesis. T EMPLATED mutations are initiated when a DNA primer strand dissociates from its cognate template and anneals with a fragment of complementary sequence in an ectopic template. The relocated primer may be extended, acquiring a short sequence that is not fully complementary to the original template, and then reanneal with its cognate template. If the acquired noncomplementary bases escape correctly oriented proofreading and mismatch repair, mutations will result. Lynn Ripley (1982) described two models for templated mutagenesis based on imperfect palindromic repeats, in one of which the ectopic template was in the other parental strand and in the other of which the ectopic template was in the daughter strand itself. Examination of other mutations added imperfect direct repeats as mutagenic templates (Ripley et al. 1986;Shinedling et al. 1987). Templated mutations are usually invoked when they simultaneously acquire multiple changes for which a plausible donor template can be found. Despite the intrinsic fascination of templated complex mutations and their potential importance for certain evolutionary paths and some human genetic disorders, the enzymology that creates them has not been characterized.Template switching also occurs in a mutation-avoiding mode called replication repair. In the canonical model for replication repair (Fujiwara and Tatsumi 1976;Higgins et al. 1976), a primer strand whose extension has been blocked by DNA damage switches to the other daughter strand as a template, extends briefly, and then switches back to its cognate template, thus accurately bypassing the damaged site.In 1987, a mechanism for su...

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Section: Resultsmentioning

confidence: 99%

Templated Mutagenesis in Bacteriophage T4 Involving Imperfect Direct or Indirect Sequence Repeats

Schultz

Drake

2008

Genetics

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“…Other studies of quasipalindrome-associated mutation have established a strand bias with respect to replication (Rosche et al 1997(Rosche et al , 1998Yoshiyama et al 2001;Yoshiyama and Maki 2003). In most cases, it is not possible to distinguish a simple intramolecular template switch in a hairpin structure from the more complex intermolecular template switch to the sister strand across the replication fork (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Insights Into Mutagenesis Using Escherichia coli Chromosomal lacZ Strains That Enable Detection of a Wide Spectrum of Mutational Events

et al. 2011

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Strand misalignments at DNA repeats during replication are implicated in mutational hotspots. To study these events, we have generated strains carrying mutations in the Escherichia coli chromosomal lacZ gene that revert via deletion of a short duplicated sequence or by template switching within imperfect inverted repeat (quasipalindrome, QP) sequences. Using these strains, we demonstrate that mutation of the distal repeat of a quasipalindrome, with respect to replication fork movement, is about 10-fold higher than the proximal repeat, consistent with more common template switching on the leading strand. The leading strand bias was lost in the absence of exonucleases I and VII, suggesting that it results from more efficient suppression of template switching by 39 exonucleases targeted to the lagging strand. The loss of 39 exonucleases has no effect on strand misalignment at direct repeats to produce deletion. To compare these events to other mutations, we have reengineered reporters (designed by Cupples and Miller 1989) that detect specific base substitutions or frameshifts in lacZ with the reverting lacZ locus on the chromosome rather than an F9 element. This set allows rapid screening of potential mutagens, environmental conditions, or genetic loci for effects on a broad set of mutational events. We found that hydroxyurea (HU), which depletes dNTP pools, slightly elevated templated mutations at inverted repeats but had no effect on deletions, simple frameshifts, or base substitutions. Mutations in nucleotide diphosphate kinase, ndk, significantly elevated simple mutations but had little effect on the templated class. Zebularine, a cytosine analog, elevated all classes.

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“…These mutations typically involve replacement of one large sequence tract (10-19 bp) with a similar-sized tract of unrelated sequence (10-28 bp). We speculated that these mutations were the result of sequence substitution mutations (Yoshiyama et al 2001). However, complementary sequences near the inserted tracts were not found, ruling this explanation out.…”

Section: Mutational Spectrum Of the Rdna Polymorphismsmentioning

confidence: 99%

Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

Ganley¹,

Kobayashi²

2007

Genome Res.

332

268

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Repeat families within genomes are often maintained with similar sequences. Traditionally, this has been explained by concerted evolution, where repeats in an array evolve "in concert" with the same sequence via continual turnover of repeats by recombination. Another form of evolution, birth-and-death evolution, can also explain this pattern, although in this case selection is the critical force maintaining the repeats. The level of intragenomic variation is the key difference between these two forms of evolution. The prohibitive size and repetitive nature of large repeat arrays have made determination of the absolute level of intragenomic repeat variability difficult, thus there is little evidence to support concerted evolution over birth-and-death evolution for many large repeat arrays. Here we use whole-genome shotgun sequence data from the genome projects of five fungal species to reveal absolute levels of sequence variation within the ribosomal RNA gene repeats (rDNA). The level of sequence variation is remarkably low. Furthermore, the polymorphisms that are detected are not functionally constrained and seem to exist beneath the level of selection. These results suggest the rDNA is evolving via concerted evolution. Comparisons with a repeat array undergoing birth-and-death evolution provide a clear contrast in the level of repeat array variation between these two forms of evolution, confirming that the rDNA indeed does evolve via concerted evolution. These low levels of intra-genomic variation are consistent with a model of concerted evolution in which homogenization is very rapid and efficiently maintains highly similar repeat arrays.[Supplemental material is available online at www.genome.org.]Repetitive elements are an abundant feature of genomes (Britten and Kohne 1968) and play critical roles in cell biology, genome structure, and adaptive evolution (Andersson et al. 1998;Shapiro and von Sternberg 2005). In many cases, repeats from a repeat family are highly similar to one another within a genome, a pattern that persists through evolutionary time even though sequence differences are apparent between species (Brown et al. 1972). Thus, the repeats seem to be maintained as a coherent family. This pattern is contrary to the expectations of conventional evolution, where repeats are expected to evolve independently ( Fig. 1) and diverge with time. This unusual mode of evolution, where repeats within a genome are more similar to each other than they are to "orthologous" repeats in a related species, is defined as concerted evolution (Zimmer et al. 1980). The molecular process responsible for concerted evolution is known as homogenization (Dover 1982), and although not fully elucidated, is thought to involve continual turnover of repeat copies by unequal recombination (e.g., Smith 1973;Szostak and Wu 1980;Kobayashi et al. 1998). However, recent studies have shown that several repeat families previously thought to evolve by concerted evolution actually evolve via a different evolutionary process known as birth-...

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Directionality of DNA replication fork movement strongly affects the generation of spontaneous mutations in Escherichia coli

Cited by 46 publications

References 18 publications

Templated Mutagenesis in Bacteriophage T4 Involving Imperfect Direct or Indirect Sequence Repeats

Templated Mutagenesis in Bacteriophage T4 Involving Imperfect Direct or Indirect Sequence Repeats

Insights Into Mutagenesis Using Escherichia coli Chromosomal lacZ Strains That Enable Detection of a Wide Spectrum of Mutational Events

Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

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