Flow cytometric analysis identifies changes in S and M phases as novel cell cycle alterations induced by the splicing inhibitor isoginkgetin
| Autor: | Kayleigh R C Rick, Erin J. Vanzyl, Alex B. Blackmore, Erin M. MacFarlane, Bruce C. McKay |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Synthesis Phase lcsh:Medicine Biochemistry S Phase chemistry.chemical_compound Spectrum Analysis Techniques Nucleic Acids RNA polymerase RNA Precursors Cell Cycle and Cell Division lcsh:Science Cyclin Multidisciplinary medicine.diagnostic_test Chemistry Cell Cycle Cell cycle Flow Cytometry Small molecule Cell biology Cell Processes Spectrophotometry RNA splicing Macrolides Cytophotometry Cell Division Research Article DNA Replication G2 Phase Spliceosome RNA Splicing Research and Analysis Methods Flow cytometry 03 medical and health sciences Cyclins medicine Biflavonoids Humans Cell Cycle Inhibitors lcsh:R G1 Phase Intron Biology and Life Sciences Cell Cycle Checkpoints Cell Biology HCT116 Cells 030104 developmental biology Spliceosomes Epoxy Compounds RNA lcsh:Q |
| Zdroj: | PLoS ONE, Vol 13, Iss 1, p e0191178 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The spliceosome is a large ribonucleoprotein complex that catalyzes the removal of introns from RNA polymerase II-transcribed RNAs. Spliceosome assembly occurs in a stepwise manner through specific intermediates referred to as pre-spliceosome complexes E, A, B, B* and C. It has been reported that small molecule inhibitors of the spliceosome that target the SF3B1 protein component of complex A lead to the accumulation of cells in the G1 and G2/M phases of the cell cycle. Here we performed a comprehensive flow cytometry analysis of the effects of isoginkgetin (IGG), a natural compound that interferes with spliceosome assembly at a later step, complex B formation. We found that IGG slowed cell cycle progression in multiple phases of the cell cycle (G1, S and G2) but not M phase. This pattern was somewhat similar to but distinguishable from changes associated with an SF3B1 inhibitor, pladienolide B (PB). Both drugs led to a significant decrease in nascent DNA synthesis in S phase, indicative of an S phase arrest. However, IGG led to a much more prominent S phase arrest than PB while PB exhibited a more pronounced G1 arrest that decreased the proportion of cells in S phase as well. We also found that both drugs led to a comparable decrease in the proportion of cells in M phase. This work indicates that spliceosome inhibitors affect multiple phases of the cell cycle and that some of these effects vary in an agent-specific manner despite the fact that they target splicing at similar stages of spliceosome assembly. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |