| Autor: |
Maksiutenko EM; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia.; St. Petersburg Branch, Vavilov Institute of General Genetics of the Russian Academy of Sciences, 199034 St. Petersburg, Russia., Barbitoff YA; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia.; Bioinformatics Institute, 197342 St. Petersburg, Russia., Danilov LG; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia., Matveenko AG; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia., Zemlyanko OM; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia.; Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia., Efremova EP; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia., Moskalenko SE; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia.; St. Petersburg Branch, Vavilov Institute of General Genetics of the Russian Academy of Sciences, 199034 St. Petersburg, Russia., Zhouravleva GA; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia.; Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia. |
| Abstrakt: |
In yeast Saccharomyces cerevisiae , there are two translation termination factors, eRF1 (Sup45) and eRF3 (Sup35), which are essential for viability. Previous studies have revealed that presence of nonsense mutations in these genes leads to amplification of mutant alleles ( sup35-n and sup45-n ), which appears to be necessary for the viability of such cells. However, the mechanism of this phenomenon remained unclear. In this study, we used RNA-Seq and proteome analysis to reveal the complete set of gene expression changes that occur during cellular adaptation to the introduction of the sup35-218 nonsense allele. Our analysis demonstrated significant changes in the transcription of genes that control the cell cycle: decreases in the expression of genes of the anaphase promoting complex APC/C ( APC9 , CDC23 ) and their activator CDC20 , and increases in the expression of the transcription factor FKH1 , the main cell cycle kinase CDC28 , and cyclins that induce DNA biosynthesis. We propose a model according to which yeast adaptation to nonsense mutations in the translation termination factor genes occurs as a result of a delayed cell cycle progression beyond the G2-M stage, which leads to an extension of the S and G2 phases and an increase in the number of copies of the mutant sup35-n allele. |
