Mechanisms of Gene Duplication and Amplification

Reams, Andrew B.; Roth, John R.

doi:10.1101/cshperspect.a016592

Cited by 196 publications

(206 citation statements)

References 101 publications

(144 reference statements)

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“…Drawing on their insightful analysis of gene duplications and amplifications in bacteria, Reams and Roth (2015) provide compelling arguments for a dynamic process leading to stable duplications/amplifications that involve multiple stages of selection defying one-step models. This may involve processes related to BIR, termed microhomology/microsatellite-induced replication, which was shown to lead to segmental duplications in yeast independent of HR or NHEJ (Payen et al 2008).…”

Section: Genome Maintenance and Human Diseasementioning

confidence: 99%

Regulation of Recombination and Genomic Maintenance

Heyer

2015

Cold Spring Harb Perspect Biol

104

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Recombination is a central process to stably maintain and transmit a genome through somatic cell divisions and to new generations. Hence, recombination needs to be coordinated with other events occurring on the DNA template, such as DNA replication, transcription, and the specialized chromosomal functions at centromeres and telomeres. Moreover, regulation with respect to the cell-cycle stage is required as much as spatiotemporal coordination within the nuclear volume. These regulatory mechanisms impinge on the DNA substrate through modifications of the chromatin and directly on recombination proteins through a myriad of posttranslational modifications (PTMs) and additional mechanisms. Although recombination is primarily appreciated to maintain genomic stability, the process also contributes to gross chromosomal arrangements and copy-number changes. Hence, the recombination process itself requires quality control to ensure high fidelity and avoid genomic instability. Evidently, recombination and its regulatory processes have significant impact on human disease, specifically cancer and, possibly, neurodegenerative diseases.

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Section: Genome Maintenance and Human Diseasementioning

confidence: 99%

Regulation of Recombination and Genomic Maintenance

Heyer

2015

Cold Spring Harb Perspect Biol

104

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“…1). The potentiating large duplications probably occur at high frequency but are likely to be very unstable (15). Such amplifications may improve growth during selection for citrate use but may be subject to rapid loss during periods of unselected growth on glucose.…”

mentioning

confidence: 99%

Reinterpreting Long-Term Evolution Experiments: Is Delayed Adaptation an Example of Historical Contingency or a Consequence of Intermittent Selection?

Roth

Maisnier‐Patin

2016

J Bacteriol

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“…Possibly, duplication mutants are intrinsically unstable and get lost. Alternatively, resistance requires more than simple duplication and might depend on further amplification into larger (unstable) arrays (32). Such duplication and amplification events may also occur at high rates under the stressful DNA replication conditions on the plate.…”

Section: Figmentioning

confidence: 99%

“…The predominance of the dupIS duplication mutants in NR18280 raised the questions of whether they are preexisting in the bacterial populations and were selected by the plating conditions. Indeed, tandem chromosomal duplications have been reported to be present in bacterial chromosomes at relatively high frequencies (31,32). Since duplication-containing mutants have a unique crossover product that should be detectable by PCR across the new junction (Fig.…”

Section: Figmentioning

confidence: 99%

Suppressors of dGTP Starvation in Escherichia coli

Itsko

Schaaper

2017

J Bacteriol

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dGTP starvation, a newly discovered phenomenon in which Escherichia coli cells are starved specifically for the DNA precursor dGTP, leads to impaired growth and, ultimately, cell death. Phenomenologically, it represents an example of nutritionally induced unbalanced growth: cell mass amplifies normally as dictated by the nutritional status of the medium, but DNA content growth is specifically impaired. The other known example of such a condition, thymineless death (TLD), involves starvation for the DNA precursor dTTP, which has been found to have important chemotherapeutic applications. Experimentally, dGTP starvation is induced by depriving an E. coli gpt optA1 strain of its required purine source, hypoxanthine. In our studies of this phenomenon, we noted the emergence of a relatively high frequency of suppressor mutants that proved resistant to the treatment. To study such suppressors, we used next-generation sequencing on a collection of independently obtained mutants. A significant fraction was found to carry a defect in the PurR transcriptional repressor, controlling de novo purine biosynthesis, or in its downstream purEK operon. Thus, upregulation of de novo purine biosynthesis appears to be a major mode of overcoming the lethal effects of dGTP starvation. In addition, another large fraction of the suppressors contained a large tandem duplication of a 250-to 300-kb genomic region that included the purEK operon as well as the acrABencoded multidrug efflux system. Thus, the suppressive effects of the duplications could potentially involve beneficial effects of a number of genes/operons within the amplified regions.IMPORTANCE Concentrations of the four precursors for DNA synthesis (2=-deoxynucleoside-5=-triphosphates [dNTPs]) are critical for both the speed of DNA replication and its accuracy. Previously, we investigated consequences of dGTP starvation, where the DNA precursor dGTP was specifically reduced to a low level. Under this condition, E. coli cells continued cell growth but eventually developed a DNA replication defect, leading to cell death due to formation of unresolvable DNA structures. Nevertheless, dGTP-starved cultures eventually resumed growth due to the appearance of resistant mutants. Here, we used whole-genome DNA sequencing to identify the responsible suppressor mutations. We show that the majority of suppressors can circumvent death by upregulating purine de novo biosynthesis, leading to restoration of dGTP to acceptable levels.

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Mechanisms of Gene Duplication and Amplification

Cited by 196 publications

References 101 publications

Regulation of Recombination and Genomic Maintenance

Regulation of Recombination and Genomic Maintenance

Reinterpreting Long-Term Evolution Experiments: Is Delayed Adaptation an Example of Historical Contingency or a Consequence of Intermittent Selection?

Suppressors of dGTP Starvation in Escherichia coli

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