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While the effects of decreased GMP synthesis have been well documented, the consequences of GMP overproduction in eukaryotes are poorly understood. In this work, we selected and characterized several mutations making yeast hypoxanthine\u2013guanine phosphoribosyltransferase insensitive to feedback inhibition by GMP. In these mutants, accumulation of guanylic nucleotides can be triggered by addition of extracellular guanine. We show that such an accumulation is highly toxic for yeast cells and results in arrest of proliferation and massive cell death. This growth defect could be partially suppressed by overexpression of Rfx1p, a transcriptional repressor of the DNA damage response pathway. Importantly, neither guanylic nucleotide toxicity nor its suppression by Rfx1p was associated with an alteration of forward mutation frequency.<\/jats:p>","DOI":"10.1534\/genetics.107.083295","type":"journal-article","created":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T01:28:41Z","timestamp":1202088521000},"page":"815-824","source":"Crossref","is-referenced-by-count":21,"title":["Lethal Accumulation of Guanylic Nucleotides in<i>Saccharomyces cerevisiae HPT1<\/i>-Deregulated Mutants"],"prefix":"10.1093","volume":"178","author":[{"given":"Annick","family":"Breton","sequence":"first","affiliation":[{"name":"Universite\u0301 Victor Segalen\/Bordeaux 2 , Institut de Biochimie et Ge\u0301ne\u0301tique Cellulaires, 33077 Bordeaux, France"},{"name":"CNRS, UMR 5095, 33077 Bordeaux, France and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoi\u0302t","family":"Pinson","sequence":"additional","affiliation":[{"name":"Universite\u0301 Victor Segalen\/Bordeaux 2 , Institut de Biochimie et Ge\u0301ne\u0301tique Cellulaires, 33077 Bordeaux, France"},{"name":"CNRS, UMR 5095, 33077 Bordeaux, France and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Coulpier","sequence":"additional","affiliation":[{"name":"IFR36, Plate-forme Transcriptome, E\u0301cole Normale Supe\u0301rieure , 75230 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-France","family":"Giraud","sequence":"additional","affiliation":[{"name":"Universite\u0301 Victor Segalen\/Bordeaux 2 , Institut de Biochimie et Ge\u0301ne\u0301tique Cellulaires, 33077 Bordeaux, France"},{"name":"CNRS, UMR 5095, 33077 Bordeaux, France and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Dautant","sequence":"additional","affiliation":[{"name":"Universite\u0301 Victor Segalen\/Bordeaux 2 , Institut de Biochimie et Ge\u0301ne\u0301tique Cellulaires, 33077 Bordeaux, France"},{"name":"CNRS, UMR 5095, 33077 Bordeaux, France and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Daignan-Fornier","sequence":"additional","affiliation":[{"name":"Universite\u0301 Victor Segalen\/Bordeaux 2 , Institut de Biochimie et Ge\u0301ne\u0301tique Cellulaires, 33077 Bordeaux, France"},{"name":"CNRS, UMR 5095, 33077 Bordeaux, France and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,2,1]]},"reference":[{"key":"2023030409452824200_","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/1471-2105-5-177","volume":"5","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"2023030409452824200_","doi-asserted-by":"crossref","first-page":"W36","DOI":"10.1093\/nar\/gki410","volume":"33","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2023030409452824200_","doi-asserted-by":"crossref","first-page":"20231","DOI":"10.1074\/jbc.R000002200","volume":"275","year":"2000","journal-title":"J. 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