Replication fork progression is paused in two large chromosomal zones flanking the <scp>DNA</scp> replication origin in <i>Escherichia coli</i>

Akiyama, Masahiro; Oshima, Taku; Chumsakul, Onuma; Ishikawa, Shu; Maki, Hisaji

doi:10.1111/gtc.12388

Cited by 3 publications

(5 citation statements)

References 32 publications

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“…We hypothesize that the process of replication initiation protects the DNA from damage and/or that newly established replication forks have a low error rate. In support of the second hypothesis, replication forks have been found to frequently pause in a 200-kb zone on either side of the origin (45), which could allow more-efficient error correction.…”

Section: Discussionmentioning

confidence: 91%

The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the Escherichia coli Chromosome Has Multiple Causes

Niccum

Lee

MohammedIsmail

et al. 2019

mBio

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Mutation accumulation experiments followed by whole-genome sequencing have revealed that, for several bacterial species, the rate of base-pair substitutions (BPSs) is not constant across the chromosome but varies in a wave-like pattern that is symmetrical about the origin of replication. The experiments reported here demonstrated that, in Escherichia coli, several interacting factors determine the wave. The origin is a major driver of BPS rates. When it is relocated, the BPS rates in a 1,000-kb region surrounding the new origin reproduce the pattern that surrounds the normal origin. However, the pattern across distant regions of the chromosome is unaltered and thus must be determined by other factors. Increasing the deoxynucleoside triphosphate (dNTP) concentration shifts the wave pattern away from the origin, supporting the hypothesis that fluctuations in dNTP pools coincident with replication firing contribute to the variations in the mutation rate. The nucleoid binding proteins (HU and Fis) and the terminus organizing protein (MatP) are also major factors. These proteins alter the three-dimensional structure of the DNA, and results suggest that mutation rates increase when highly structured DNA is replicated. Biases in error correction by proofreading and mismatch repair, both of which may be responsive to dNTP concentrations and DNA structure, also are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates. IMPORTANCE It has been found in several species of bacteria that the rate at which single base pairs are mutated is not constant across the genome but varies in a wave-like pattern that is symmetrical about the origin of replication. Using Escherichia coli as our model system, we show that this pattern is the result of several interconnected factors. First, the timing and progression of replication are important in determining the wave pattern. Second, the three-dimensional structure of the DNA is also a factor, and the results suggest that mutation rates increase when highly structured DNA is replicated. Finally, biases in error correction, which may be responsive both to the progression of DNA synthesis and to DNA structure, are major determinants of the wave pattern. These factors should apply to most bacterial and, possibly, eukaryotic genomes and suggest that different areas of the genome evolve at different rates.

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Section: Discussionmentioning

confidence: 91%

The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the Escherichia coli Chromosome Has Multiple Causes

Niccum

Lee

MohammedIsmail

et al. 2019

mBio

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“…of sequences where replication forks have stalled or paused, detected as an increase in BrdU signal. Accumulations of BrdU signal representing hotspots where replication forks stall/pause has been previously found in bacteria [17] and can be identified as a BrdU peak using a bioinformatic peak calling procedure (Fig. 1B).…”

Section: Identification Of Replication Fork Stalling/pausing Sitesmentioning

confidence: 79%

“…If a hotspot occurred in all cells, there would be a total decline in BrdU incorporation downstream of the replication fork stalling/pausing site; however, if a hotspot arose only in a fraction of the cells, there would be an overrepresentation of sequences where replication forks have stalled or paused, detected as an increase in BrdU signal. Accumulations of BrdU signal representing hotspots where replication forks stall/pause has been previously found in bacteria [ 17 ] and can be identified as a BrdU peak using a bioinformatic peak calling procedure (Fig. 1 B).…”

Section: Resultsmentioning

confidence: 95%

Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression

Rojas,

Wang,

Guglielmi

et al. 2024

Genome Biol

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Background DNA replication progression can be affected by the presence of physical barriers like the RNA polymerases, leading to replication stress and DNA damage. Nonetheless, we do not know how transcription influences overall DNA replication progression. Results To characterize sites where DNA replication forks stall and pause, we establish a genome-wide approach to identify them. This approach uses multiple timepoints during S-phase to identify replication fork/stalling hotspots as replication progresses through the genome. These sites are typically associated with increased DNA damage, overlapped with fragile sites and with breakpoints of rearrangements identified in cancers but do not overlap with replication origins. Overlaying these sites with a genome-wide analysis of RNA polymerase II transcription, we find that replication fork stalling/pausing sites inside genes are directly related to transcription progression and activity. Indeed, we find that slowing down transcription elongation slows down directly replication progression through genes. This indicates that transcription and replication can coexist over the same regions. Importantly, rearrangements found in cancers overlapping transcription-replication collision sites are detected in non-transformed cells and increase following treatment with ATM and ATR inhibitors. At the same time, we find instances where transcription activity favors replication progression because it reduces histone density. Conclusions Altogether, our findings highlight how transcription and replication overlap during S-phase, with both positive and negative consequences for replication fork progression and genome stability by the coexistence of these two processes.

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“…Additionally, these distributions are useful for representing known coverage depth characteristics. For example, some researchers have described non-linear coverage depth trends over genome sequences in both bacteria and archaea (Chen et al, 2005;Watanabe et al, 2012;Hawkins et al, 2013;Pelve et al, 2013;Rudolph et al, 2013;Wendel, Courcelle & Courcelle, 2014;Wu et al, 2014;Maduike et al, 2014;Yang et al, 2015;Akiyama et al, 2016;Ohbayashi et al, 2016;Forsyth et al, 2018;Retkute et al, 2018). It was expected that this trend could be quantified by extension for the distributions proposed in the previous studies.…”

Section: Statistical Model To Estimate Replication Ratementioning

confidence: 94%

“…Third, the characteristics of coverage depth distributions themselves have not been sufficiently investigated. Some previous studies have reported non-linear DNA quantity trends (Hawkins et al, 2013;Pelve et al, 2013;Wu et al, 2014;Akiyama et al, 2016), such as those including a significant increase around the replication origin. Based on these studies, it has been suggested that replication affects not only the ratio of maximum to minimum depth, but also changes the degree of density around the replication origin.…”

Section: Introductionmentioning

confidence: 97%

Probabilistic model based on circular statistics for quantifying coverage depth dynamics originating from DNA replication

Suzuki

Yamada

2020

PeerJ

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Background With the development of DNA sequencing technology, static omics profiling in microbial communities, such as taxonomic and functional gene composition determination, has become possible. Additionally, the recently proposed in situ growth rate estimation method allows the applicable range of current comparative metagenomics to be extended to dynamic profiling. However, with this method, the applicable target range is presently limited. Furthermore, the characteristics of coverage depth during replication have not been sufficiently investigated. Results We developed a probabilistic model that mimics coverage depth dynamics. This statistical model explains the bias that occurs in the coverage depth due to DNA replication and errors that arise from coverage depth observation. Although our method requires a complete genome sequence, it involves a stable to low coverage depth (>0.01×). We also evaluated the estimation using real whole-genome sequence datasets and reproduced the growth dynamics observed in previous studies. By utilizing a circular distribution in the model, our method facilitates the quantification of unmeasured coverage depth features, including peakedness, skewness, and degree of density, around the replication origin. When we applied the model to time-series culture samples, the skewness parameter, which indicates the asymmetry, was stable over time; however, the peakedness and degree of density parameters, which indicate the concentration level at the replication origin, changed dynamically. Furthermore, we demonstrated the activity measurement of multiple replication origins in a single chromosome. Conclusions We devised a novel framework for quantifying coverage depth dynamics. Our study is expected to serve as a basis for replication activity estimation from a broader perspective using the statistical model.

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Replication fork progression is paused in two large chromosomal zones flanking the DNA replication origin in Escherichia coli

Cited by 3 publications

References 32 publications

The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the Escherichia coli Chromosome Has Multiple Causes

The Symmetrical Wave Pattern of Base-Pair Substitution Rates across the Escherichia coli Chromosome Has Multiple Causes

Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression

Probabilistic model based on circular statistics for quantifying coverage depth dynamics originating from DNA replication

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