scholarly journals DNA Replication-transcription conflicts do not significantly contribute to spontaneous mutations due to replication errors in Escherichia coli

2021 ◽  
Author(s):  
Patricia L Foster ◽  
Brittany A Niccum ◽  
Heewook Lee
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Base Pair ◽  
Point Mutations ◽  
Trna Genes ◽  
Small Indels ◽  
Replication Errors ◽  
Highly Expressed Genes ◽  
Genomic Locations ◽  
Orientation Bias

Encounters between DNA replication and transcription can cause genomic disruption, particularly when the two meet head-on. Whether these conflicts produce point mutations is debated. This paper presents detailed analyses of a large collection of mutations generated during mutation accumulation experiments with mismatch-repair (MMR) defective Escherichia coli. With MMR absent, mutations are primarily due to DNA replication errors. Overall, there were no differences in the frequencies of base-pair substitutions or small indels (insertion and deletions ≤ 4 bp) in the coding sequences or promoters of genes oriented codirectionally versus head-on to replication. Among a subset of highly expressed genes there was a 2- to 3-fold bias for indels in genes oriented head-on to replication, but this difference was almost entirely due to the asymmetrical genomic locations of tRNA genes containing mononucleotide runs, which are hotspots for indels.No additional orientation bias in mutation frequencies occurred when MMR-strains were also defective for transcription-coupled repair (TCR). However, in contrast to other reports, loss of TCR slightly increased the overall mutation rate, meaning that TCR is antimutagenic. There was no orientation bias in mutation frequencies among the stress-response genes that are regulated by RpoS or induced by DNA damage. Thus, biases in the locations of mutational targets can account for most, if not all, apparent biases in mutation frequencies between genes oriented head-on versus co-directional to replication. In addition, the data revealed a strong correlation of the frequency of base-pair substitutions with gene length, but no correlation with gene expression levels.

scholarly journals Spontaneous mutation in Escherichia coli containing the dnaE911 DNA polymerase antimutator allele.

Genetics ◽  
1994 ◽  
Vol 138 (2) ◽  
pp. 263-270 ◽  
Author(s):  
A R Oller ◽  
R M Schaaper
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Mismatch Repair ◽  
Dna Polymerase ◽  
Spontaneous Mutation ◽  
Gene Encoding ◽  
Replication Errors ◽  
Lac Operator ◽  
Laci Gene ◽  
Dna Replication Errors

Abstract We have previously isolated mutants of Escherichia coli that replicate their DNA with increased fidelity. These mutants have a mutation in the dnaE gene, encoding the alpha subunit of DNA polymerase III. They were isolated in a mismatch-repair-defective mutL background, in which mutations can be considered to represent uncorrected DNA replication errors. In the present study we analyze the effect of one of these alleles, dnaE911, on spontaneous mutagenesis in a mismatch-repair-proficient background. In this background, spontaneous mutations may be the sum of uncorrected replication errors and mutations resulting from other pathways. Hence, the effect of the dnaE allele may provide insights into the contribution of uncorrected DNA replication errors to spontaneous mutation. The data show that dnaE911 decreases the level of Rifr, lacI and galK mutations in this background by 1.5-2-fold. DNA sequencing of 748 forward mutants in the lacI gene reveals that this effect has a clear specificity. Transversions are decreased by approximately 3-fold, whereas transitions, frameshifts, deletions and duplications remain essentially unchanged. Among the transversions, A.T-->T.A are affected most strongly (approximately 6-fold). In addition to this effect on transversions within the lacI gene, one previously recognized A.T-->G.C base-pair substitution hotspot in the lac operator is also reduced (approximately 5-fold). The data are discussed in the light of the role of DNA replication errors in spontaneous mutation, as well as other possible explanations for the observed antimutator effects.

scholarly journals DNA Replication-Transcription Conflicts Do Not Significantly Contribute to Spontaneous Mutations Due to Replication Errors in Escherichia coli

mBio ◽  
2021 ◽  
Author(s):  
Patricia L. Foster ◽  
Brittany A. Niccum ◽  
Heewook Lee
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Spontaneous Mutations ◽  
Replication Errors ◽  
Dna Template ◽  
Two Machines

Because DNA replication and transcription occur on the same DNA template, encounters between the two machines occur frequently. When these encounters are head-to-head, genomic disruption can occur.

scholarly journals Lack of Strand Bias in UV-Induced Mutagenesis in Escherichia coli

2002 ◽  
Vol 184 (16) ◽  
pp. 4449-4454 ◽  
Author(s):  
Damian Gawel ◽  
Magdalena Maliszewska-Tkaczyk ◽  
Piotr Jonczyk ◽  
Roel M. Schaaper ◽  
Iwona J. Fijalkowska
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Target Sequence ◽  
Induced Mutations ◽  
Replication Errors ◽  
Origin Of Dna Replication ◽  
Mutator Effect ◽  
Induced Mutagenesis ◽  
Leading Strand ◽  
Other Orientation

ABSTRACT We have investigated whether UV-induced mutations are created with equal efficiency on the leading and lagging strands of DNA replication. We employed an assay system that permits measurement of mutagenesis in the lacZ gene in pairs of near-identical strains. Within each pair, the strains differ only in the orientation of the lacZ gene with respect to the origin of DNA replication. Depending on this orientation, any lacZ target sequence will be replicated in one orientation as a leading strand and as a lagging strand in the other orientation. In contrast to previous results obtained for mutations resulting from spontaneous replication errors or mutations resulting from the spontaneous SOS mutator effect, measurements of UV-induced mutagenesis in uvrA strains fail to show significant differences between the two target orientations. These data suggest that SOS-mediated mutagenic translesion synthesis on the Escherichia coli chromosome may occur with equal or similar probability on leading and lagging strands.

Escherichia coli Mutator ΔpolA is Defective in Base Mismatch Correction: The Nature of in Vivo DNA Replication Errors

2005 ◽  
Vol 351 (2) ◽  
pp. 299-308 ◽  
Author(s):  
Yu-ichiro Tago ◽  
Masaru Imai ◽  
Makoto Ihara ◽  
Hironari Atofuji ◽  
Yuki Nagata ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Replication Errors ◽  
Mismatch Correction ◽  
Base Mismatch ◽  
Dna Replication Errors

scholarly journals Mechanisms of activation of the cryptic cel operon of Escherichia coli K12.

Genetics ◽  
1990 ◽  
Vol 124 (3) ◽  
pp. 473-482 ◽  
Author(s):  
L L Parker ◽  
B G Hall
Keyword(s):  
Escherichia Coli ◽  
Base Pair ◽  
Point Mutations ◽  
Insertion Sequences ◽  
Wild Type ◽  
Single Base ◽  
Escherichia Coli K12 ◽  
In The Wild ◽  
Single Base Pair ◽  
Strain Dependent

Abstract The cel (cellobiose utilization) operon of Escherichia coli K12 is not expressed in the wild-type organism. However, mutants that can express the operon and thereby utilize the beta-glucoside sugars cellobiose, arbutin and salicin are easily isolated. Two kinds of mutations are capable of activating the operon. The first involves mutations that allow the repressor to recognize the substrates cellobiose, arbutin and salicin as inducers. We have identified the sequence changes in five different active alleles and found those differences to be single base pair changes at one of two lysine codons in the repressor gene. The second kind of mutation involves the integration of the insertion sequences IS1, IS2 or IS5 into a 108-bp region 72-180 bp upstream of the start of transcription. Integration occurs at several different sites and in different orientations. Transcription of the cel operon begins at the same base pair in all mutants examined. Of 44 independent cel+ mutants, 27 were activated by point mutations and 17 were activated by insertion sequences. The preferred mechanism of activation appears to be strain dependent, since one of the parents yielded 94% insertionally activated alleles, while another yielded 100% point mutation activated alleles.

DNA Replication Errors Produced by the Replicative Apparatus of Escherichia coli

1999 ◽  
Vol 289 (4) ◽  
pp. 835-850 ◽  
Author(s):  
Shingo Fujii ◽  
Masahiro Akiyama ◽  
Kazuhiro Aoki ◽  
Yutaka Sugaya ◽  
Kumiko Higuchi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Replication Errors ◽  
Dna Replication Errors
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