Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5589124 | Gene | 2017 | 26 Pages |
Abstract
Previous reports and our recently published data indicated that some enzymes of glycolysis and the tricarboxylic acid cycle can affect the genome replication process by changing either the efficiency or timing of DNA synthesis in human normal cells. Both these pathways are connected with the pentose phosphate pathway (PPP pathway). The PPP pathway supports cell growth by generating energy and precursors for nucleotides and amino acids. Therefore, we asked if silencing of genes coding for enzymes involved in the pentose phosphate pathway may also affect the control of DNA replication in human fibroblasts. Particular genes coding for PPP pathway enzymes were partially silenced with specific siRNAs. Such cells remained viable. We found that silencing of the H6PD, PRPS1, RPE genes caused less efficient enterance to the S phase and decrease in efficiency of DNA synthesis. On the other hand, in cells treated with siRNA against G6PD, RBKS and TALDO genes, the fraction of cells entering the S phase was increased. However, only in the case of G6PD and TALDO, the ratio of BrdU incorporation to DNA was significantly changed. The presented results together with our previously published studies illustrate the complexity of the influence of genes coding for central carbon metabolism on the control of DNA replication in human fibroblasts, and indicate which of them are especially important in this process.
Keywords
PRPsG6PPGMPGLSTKTXu5PR5PS7PPFKF6PG6PDD-riboseBrdU incorporationPRPPE4PDERARU5P6PG6PGLrPIH6PDGPiG3PRPEPGD6-phosphogluconate dehydrogenase6-phosphogluconateAldoAldolaseErythrose 4-phosphateBrdUbromodeoxyuridineTransaldolaseTransketolaseribose 5-phosphateRibokinaseribulose 5-phosphatexylulose 5-phosphatesedoheptulose 7-phosphateFructose 6-phosphatePhosphofructokinasephosphoglucomutaseHuman fibroblastspentose phosphate pathwayHexose-6-phosphate dehydrogenasehexokinaseTCA cycletricarboxylic acid cycleGlucose-6-phosphate isomeraseglucose-6-phosphate dehydrogenaseglyceraldehyde 3-phosphate
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Biochemistry, Genetics and Molecular Biology
Genetics
Authors
Karolina Fornalewicz, Aneta Wieczorek, Grzegorz WÄgrzyn, Robert ÅyżeÅ,