دورية أكاديمية
Stimulation of mutagenesis by proportional deoxyribonucleoside triphosphate accumulation in Escherichia coli.
| العنوان: | Stimulation of mutagenesis by proportional deoxyribonucleoside triphosphate accumulation in Escherichia coli. |
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| المؤلفون: | Wheeler LJ; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, 97331-7305, USA., Rajagopal I, Mathews CK |
| المصدر: | DNA repair [DNA Repair (Amst)] 2005 Dec 08; Vol. 4 (12), pp. 1450-6. Date of Electronic Publication: 2005 Oct 03. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101139138 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1568-7864 (Print) Linking ISSN: 15687856 NLM ISO Abbreviation: DNA Repair (Amst) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier, c2002- |
| مواضيع طبية MeSH: | Mutagenesis*/drug effects, Deoxyribonucleotides/*metabolism , Escherichia coli/*genetics , Escherichia coli/*metabolism, Bacterial Proteins/genetics ; Base Pair Mismatch ; Cycloserine/pharmacology ; DNA Replication ; DNA-Directed DNA Polymerase/metabolism ; Escherichia coli/drug effects ; Kinetics ; Mutation/genetics ; Ribonucleotide Reductases/genetics ; Ribonucleotide Reductases/metabolism ; SOS Response, Genetics ; Serine Endopeptidases/genetics |
| مستخلص: | Intracellular pool sizes of deoxyribonucleoside triphosphates (dNTPs) are highly regulated. Unbalanced dNTP pools, created by abnormal accumulation or deficiency of one nucleotide, are known to be mutagenic and to have other genotoxic consequences. Recent studies in our laboratory on DNA replication in vitro suggested that balanced accumulation of dNTPs, in which all four pools increase proportionately, also stimulates mutagenesis. In this paper, we ask whether proportional dNTP pool increases are mutagenic also in living cells. Escherichia coli was transformed with recombinant plasmids that overexpress E. coli genes nrdA and nrdB, which encode the two protein subunits of aerobic ribonucleotide reductase. Roughly proportional dNTP pool expansion, by factors of 2- to 6-fold in different experiments, was accompanied by increases in spontaneous mutation frequency of up to 40-fold. Expression of a catalytically inactive ribonucleotide reductase had no effect on either dNTP pools or mutagenesis, suggesting that accumulation of dNTPs is responsible for the increased mutagenesis. Preliminary experiments with strains defective in SOS regulon induction suggest a requirement for one or more SOS functions in the dNTP-enhanced mutagenesis. Because a replisome extending from correctly matched 3'-terminal nucleotides is almost certainly saturated with dNTP substrates in vivo, whereas chain extension from mismatched nucleotides almost certainly proceeds at sub-saturating rates, we propose that the mutagenic effect of proportional dNTP pool expansion is preferential stimulation of chain extension from mismatches as a result of increases in intracellular dNTP concentrations. |
| معلومات مُعتمدة: | ES00210 United States ES NIEHS NIH HHS |
| المشرفين على المادة: | 0 (Bacterial Proteins) 0 (Deoxyribonucleotides) 0 (LexA protein, Bacteria) 95IK5KI84Z (Cycloserine) EC 1.17.4.- (Ribonucleotide Reductases) EC 2.7.7.7 (DNA-Directed DNA Polymerase) EC 3.4.21.- (Serine Endopeptidases) |
| تواريخ الأحداث: | Date Created: 20051007 Date Completed: 20060203 Latest Revision: 20191210 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.dnarep.2005.09.003 |
| PMID: | 16207537 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1568-7864 |
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| DOI: | 10.1016/j.dnarep.2005.09.003 |