The Gene for Nucleoside Diphosphate Kinase Functions as a Mutator Gene inEscherichia coli

Lü, Qing; Zhang, Xiaolin; Almaula, Niva; Mathews, Christopher K.; Inouye, Masayori

doi:10.1006/jmbi.1995.0620

Cited by 102 publications

(140 citation statements)

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“…Loss of nucleotide diphosphate kinase activity encoded by the ndk gene has been shown to cause a strong mutator phenotype (Lu et al 1995;Miller et al 2002), especially for AT to TA transversions (CC105) and 11G frameshifts (CC107), which we confirm here with chromosomal lacZ reversion reporters. The source of mutagenic effect is unclear but there is modest elevation of dCTP and reduction of dATP pools in ndk mutants (Shen et al 2006); another study correlated ndk mutagenicity with dUTP incorporation into DNA (Nordman and Wright 2008).…”

Section: Discussionsupporting

confidence: 84%

“…Such strains are viable but exhibit a strong mutator phenotype (Lu et al 1995;Miller et al 2002), possibly due to perturbations of nucleotide pools, including a modest elevation of dCTP and diminishment of dATP (Shen et al 2006) or accumulation of dUTP (Nordman and Wright 2008). We transduced an ndk knockout allele into our AT to TA and 11G reporter strains [which are strongly affected by ndk on F9 lac (CC105 and CC107); Miller et al 2002], as well as into the 211 deletion and QP5 reporters.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 84%

Section: Resultsmentioning

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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“…Neuroendocrine differentiation followed transfection of the murine phaeochromocytoma PC12 cell line with nm23 (35). Furthermore, nm23 influences genome stability as a mutator phenotype is present in knockout strains of bacteria (36,37). In addition, particularly in unicellular lineages of cells, Nm23 expression often correlates with proliferation and lack of differentiation (reviewed in Ref.…”

Section: Discussionmentioning

confidence: 99%

Nm23/PuF Does Not Directly Stimulate Transcription through the CT Element in Vivo

Michelotti

Sanford

Freije

et al. 1997

Journal of Biological Chemistry

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“…The disruption of an Nme ortholog in E. coli was reported to produce a mutator phenotype and thus was opening research in that field (Lu et al 1995). Due to artifactual binding of Nme to DNA and DNAbinding proteins, this line of research has been fraught with missteps but, recently, some consistent patterns have emerged.…”

Section: Nme1 As Metastasis Suppressormentioning

confidence: 99%

Progress on Nme (NDP kinase/Nm23/Awd) gene family-related functions derived from animal model systems: studies on development, cardiovascular disease, and cancer metastasis exemplified

Hsu

Steeg

Zollo

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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The Gene for Nucleoside Diphosphate Kinase Functions as a Mutator Gene inEscherichia coli

Cited by 102 publications

References 0 publications

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

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

Nm23/PuF Does Not Directly Stimulate Transcription through the CT Element in Vivo

Progress on Nme (NDP kinase/Nm23/Awd) gene family-related functions derived from animal model systems: studies on development, cardiovascular disease, and cancer metastasis exemplified

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