{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:08:23Z","timestamp":1791317303339,"version":"4.3.1"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T00:00:00Z","timestamp":1497484800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["Z01 ES101905"],"award-info":[{"award-number":["Z01 ES101905"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2017,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            dGTP starvation, a newly discovered phenomenon in which\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n            <jats:italic>gpt optA1<\/jats:italic>\n            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\n            <jats:italic>de novo<\/jats:italic>\n            purine biosynthesis, or in its downstream\n            <jats:italic>purEK<\/jats:italic>\n            operon. Thus, upregulation of\n            <jats:italic>de novo<\/jats:italic>\n            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\n            <jats:italic>purEK<\/jats:italic>\n            operon as well as the\n            <jats:italic>acrAB<\/jats:italic>\n            -encoded 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.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Concentrations of the four precursors for DNA synthesis (2\u2032-deoxynucleoside-5\u2032-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,\n            <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n            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\n            <jats:italic>de novo<\/jats:italic>\n            biosynthesis, leading to restoration of dGTP to acceptable levels.\n          <\/jats:p>","DOI":"10.1128\/jb.00142-17","type":"journal-article","created":{"date-parts":[[2017,4,4]],"date-time":"2017-04-04T00:30:45Z","timestamp":1491265845000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Suppressors of dGTP Starvation in Escherichia coli"],"prefix":"10.1128","volume":"199","author":[{"given":"Mark","family":"Itsko","sequence":"first","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel M.","family":"Schaaper","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Control of macromolecular synthesis: a study of DNA, RNA, and protein synthesis, in bacteria","author":"Maal\u00f8e O","year":"1966","unstructured":"Maal\u00f8e O Kjeldgaard NO . 1966. 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