Silencing of the pentose phosphate pathway genes influences DNA replication in human fibroblasts
Karolina Fornalewicz , Aneta Wieczorek , Grzegorz Węgrzyn , Robert Łyżeń
AbstractPrevious 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.
|Journal series||Gene, ISSN 0378-1119, (A 20 pkt)|
|Publication size in sheets||0.5|
|Keywords in English||PPP pathway, DNA replication, control S phase of the cell cycle, BrdU incorporation, human fibroblasts|
|Score|| = 20.0, 02-03-2019, ArticleFromJournal|
= 20.0, 02-03-2019, ArticleFromJournal
|Publication indicators||= 3; : 2017 = 2.498 (2) - 2017=2.217 (5)|
|Citation count*||3 (2019-03-22)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.