<i>uvrD</i> mutations enhance tandem repeat deletion in the <i>Escherichia coli</i> chromosome via SOS induction of the RecF recombination pathway

Bierne, Hélène; Seigneur, M.; Sd, Ehrlich; Michel, Bertrand

doi:10.1046/j.1365-2958.1997.6011973.x

Cited by 57 publications

(56 citation statements)

References 35 publications

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“…The expression of sulA-lac in a uvrD strain remained elevated despite introduction of mutations in recB, recF, recQ, or ruvABC (data not shown). Substantially similar results have also been described earlier (3).…”

Section: Vol 182 2000 Uvrd-lon Incompatibility In E Coli 3153supporting

confidence: 80%

“…Another substrate of the Lon protease is the cell septation inhibitor SulA, whose synthesis is induced during the SOS response; as a consequence, lon mutants are known to be sensitive to SOS-inducing agents (reviewed in references 23 and 55). At least some uvrD mutations have been shown earlier to induce the SOS response (3,25,38), and we therefore tested the hypothesis that the uvrD-lon combination is rendered inviable because Lon becomes essential to degrade the increased concentration of SulA in the uvrD mutant background. (i) Using sulA-lac expression as a measure of SOS induction, we found that the uvrD400::Tn10dTet insertion (which is lon incompatible) caused a moderate (5-fold) induction of the SOS regulon, as against the 70-fold increase observed in a fully derepressed (⌬lexA) strain ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

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lon Incompatibility Associated with Mutations Causing SOS Induction: Null uvrD Alleles Induce an SOS Response in Escherichia coli

2000

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The uvrD gene in Escherichia coli encodes a 720-amino-acid 3-5 DNA helicase which, although nonessential for viability, is required for methyl-directed mismatch repair and nucleotide excision repair and furthermore is believed to participate in recombination and DNA replication. We have shown in this study that null mutations in uvrD are incompatible with lon, the incompatibility being a consequence of the chronic induction of SOS in uvrD strains and the resultant accumulation of the cell septation inhibitor SulA (which is a normal target for degradation by Lon protease). uvrD-lon incompatibility was suppressed by sulA, lexA3(Ind ؊ ), or recA (Def) mutations. Other mutations, such as priA, dam, polA, and dnaQ (mutD) mutations, which lead to persistent SOS induction, were also lon incompatible. SOS induction was not observed in uvrC and mutH (or mutS) mutants defective, respectively, in excision repair and mismatch repair. Nor was uvrD-mediated SOS induction abolished by mutations in genes that affect mismatch repair (mutH), excision repair (uvrC), or recombination (recB and recF). These data suggest that SOS induction in uvrD mutants is not a consequence of defects in these three pathways. We propose that the UvrD helicase participates in DNA replication to unwind secondary structures on the lagging strand immediately behind the progressing replication fork, and that it is the absence of this function which contributes to SOS induction in uvrD strains.DNA helicases are enzymes involved in a variety of processes such as DNA replication, repair, and recombination, and at least 12 have been identified in Escherichia coli (29,30). Of these, only DnaB helicase (with 5Ј-3Ј polarity) is essential for cell viability, being associated with movement of the chromosome replication fork (27). Three other helicases, Rep, PriA, and UvrD, each with 3Ј-5Ј polarity, have also been suggested to participate in chromosome replication, but their roles are not as well established.The UvrD helicase (also called helicase II) is the product of the uvrD gene and is a polypeptide of 720 amino acids. UvrD is required in the pathways of both methyl-directed mismatch repair (34, 35) and UvrABC-mediated excision repair (46, 47), and uvrD mutants exhibit a spontaneous mutator phenotype as well as increased sensitivity to UV irradiation. Genetic evidence has implicated UvrD in homologous recombination (21,23,26,32). The suggestion has also been made that UvrD participates in DNA replication, based on (i) experiments with cell-free systems (17, 22), (ii) the observation that uvrD null mutations are incompatible with rep (encoding the Rep helicase) or polA (encoding DNA polymerase I) mutations (56), and (iii) identification of dominant-lethal uvrD mutations (8,59).In the present study, we discovered that lon (encoding the Lon protease) represents a third locus, mutations in which are incompatible with uvrD null alleles. Chronic induction of the SOS response (reviewed in references 23 and 55) in the uvrD null strains was shown to be the basis for l...

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Section: Vol 182 2000 Uvrd-lon Incompatibility In E Coli 3153supporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

lon Incompatibility Associated with Mutations Causing SOS Induction: Null uvrD Alleles Induce an SOS Response in Escherichia coli

2000

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“…3). Stimulation of tandem repeat instability in a uvrD mutant was previously shown to be caused by an increase in RecF-mediated recombination (21) and this result may relate to the antirecombination role of the UvrD protein (22).…”

Section: Resultsmentioning

confidence: 99%

DNA tandem repeat instability in the Escherichia coli chromosome is stimulated by mismatch repair at an adjacent CAG·CTG trinucleotide repeat

Blackwood

Okely²,

Zahra³

et al. 2010

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

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Approximately half the human genome is composed of repetitive DNA sequences classified into microsatellites, minisatellites, tandem repeats, and dispersed repeats. These repetitive sequences have coevolved within the genome but little is known about their potential interactions. Trinucleotide repeats (TNRs) are a subclass of microsatellites that are implicated in human disease. Expansion of CAG·CTG TNRs is responsible for Huntington disease, myotonic dystrophy, and a number of spinocerebellar ataxias. In yeast DNA double-strand break (DSB) formation has been proposed to be associated with instability and chromosome fragility at these sites and replication fork reversal (RFR) to be involved either in promoting or in preventing instability. However, the molecular basis for chromosome fragility of repetitive DNA remains poorly understood. Here we show that a CAG·CTG TNR array stimulates instability at a 275-bp tandem repeat located 6.3 kb away on the Escherichia coli chromosome. Remarkably, this stimulation is independent of both DNA double-strand break repair (DSBR) and RFR but is dependent on a functional mismatch repair (MMR) system. Our results provide a demonstration, in a simple model system, that MMR at one type of repetitive DNA has the potential to influence the stability of another. Furthermore, the mechanism of this stimulation places a limit on the universality of DSBR or RFR models of instability and chromosome fragility at CAG·CTG TNR sequences. Instead, our data suggest that explanations of chromosome fragility should encompass the possibility of chromosome gaps formed during MMR.DNA repair | DNA replication | fragile site

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“…Thus, Dda may mediate deletion mutagenesis in response to DNA damage, and overproduction of Dda might promote deletions between repetitive sequences. Indeed, overproduction of UvrD, a helicase unrelated to Dda, promotes deletions between tandem repeats via induction of the RecF recombination pathway (28).…”

Section: Resultsmentioning

confidence: 99%

UvsX Recombinase and Dda Helicase Rescue Stalled Bacteriophage T4 DNA Replication Forks in Vitro

Kadyrov¹,

Drake

2004

Journal of Biological Chemistry

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The rescue of stalled replication forks via a series of steps that include fork regression, template switching, and fork restoration often has been proposed as a major mechanism for accurately bypassing non-coding DNA lesions. Bacteriophage T4 encodes almost all of the proteins required for its own DNA replication, recombination, and repair. Both recombination and recombination repair in T4 rely on UvsX, a RecA-like recombinase. We show here that UvsX plus the T4-encoded helicase Dda suffice to rescue stalled T4 replication forks in vitro. This rescue is based on two sequential template-switching reactions that allow DNA replication to bypass a non-coding DNA lesion in a non-mutagenic manner.DNA template-strand lesions that prevent the extension of primer strands are usually lethal. Four general mechanisms operate to overcome such lethality: direct repair that regenerates a native structure (e.g. photoreaction and dealkylation), excision repair that replaces damaged bases or deoxyribose residues, translesion synthesis that is usually mutation-prone, and recombination repair that accurately bypasses DNA damage.The essence of recombination repair is that it derives accurate genetic information from the nascent sister chromatid (or from a homologous chromosome when repairing a double strand break); excision repair, on the other hand, derives the requisite genetic information from the complementary strand of the same double helix. Recombination repair was first characterized in Escherichia coli (1-4). The classical E. coli breakreunion model holds that blocked primer extension is followed by downstream reinitiation, leaving a gap that is then filled at least in part by the physical donation of a strand of appropriate polarity cut from the sister chromatid. The donating strand gap is filled by DNA synthesis, whereas the blocking lesion remains as a problem for the future.Recent progress in understanding recombination repair, based mainly on work with E. coli, has highlighted its importance for rescuing replication forks stalled at sites of DNA damage or spontaneous fork collapse (8 -11). One model of recombination repair (Fig. 1) invokes a topological rearrangement in which the fork regresses into a configuration in which the parental strands reanneal and the two daughter strands anneal. This rearrangement generates a structure that constitutes a Holliday junction and that to some resembles a chicken foot (12). In the case of a primer strand whose extension is blocked by a lesion in the template strand, fork regression provides a template that allows limited primer extension. Subsequent reformation of a conventional replication fork then provides a primer strand that has accurately bypassed the template lesion. This pathway was named replication repair and was initially suggested to occur during mammalian DNA replication (5). It was later validated by genetical and enzymological analyses in phage T4 (6, 7).In addition to a DNA polymerase, the canonical model of replication repair (Fig. 1) immediately suggests roles f...

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uvrD mutations enhance tandem repeat deletion in the Escherichia coli chromosome via SOS induction of the RecF recombination pathway

Cited by 57 publications

References 35 publications

lon Incompatibility Associated with Mutations Causing SOS Induction: Null uvrD Alleles Induce an SOS Response in Escherichia coli

lon Incompatibility Associated with Mutations Causing SOS Induction: Null uvrD Alleles Induce an SOS Response in Escherichia coli

DNA tandem repeat instability in the Escherichia coli chromosome is stimulated by mismatch repair at an adjacent CAG·CTG trinucleotide repeat

UvsX Recombinase and Dda Helicase Rescue Stalled Bacteriophage T4 DNA Replication Forks in Vitro

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