| Autor: |
Zhuk AS; Institute of Applied Computer Science, ITMO University, 191002 St. Petersburg, Russia.; Vavilov Institute of General Genetics, St. Petersburg Branch, Russian Academy of Sciences, 199034 St. Petersburg, Russia.; Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia., Shiriaeva AA; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia., Andreychuk YV; Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia., Kochenova OV; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia.; Howard Hughes Medical Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA 02115, USA., Tarakhovskaya ER; Vavilov Institute of General Genetics, St. Petersburg Branch, Russian Academy of Sciences, 199034 St. Petersburg, Russia.; Department of Plant Physiology and Biochemistry, St. Petersburg State University, 199034 St. Petersburg, Russia., Bure VM; Faculty of Applied Mathematics and Control Processes, St. Petersburg State University, 199034 St. Petersburg, Russia., Pavlov YI; Eppley Institute for Research in Cancer, Fred and Pamela Buffett Cancer Center, the University of Nebraska Medical Center, Omaha, NE 68198, USA.; Departments of Biochemistry and Molecular Biology, Microbiology and Pathology, Genetics Cell Biology and Anatomy, the University of Nebraska Medical Center, Omaha, NE 68198, USA., Inge-Vechtomov SG; Vavilov Institute of General Genetics, St. Petersburg Branch, Russian Academy of Sciences, 199034 St. Petersburg, Russia.; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia., Stepchenkova EI; Vavilov Institute of General Genetics, St. Petersburg Branch, Russian Academy of Sciences, 199034 St. Petersburg, Russia.; Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia. |
| Abstrakt: |
Spontaneous or induced DNA lesions can result in stable gene mutations and chromosomal aberrations due to their inaccurate repair, ultimately resulting in phenotype changes. Some DNA lesions per se may interfere with transcription, leading to temporary phenocopies of mutations. The direct impact of primary DNA lesions on phenotype before their removal by repair is not well understood. To address this question, we used the alpha-test, which allows for detecting various genetic events leading to temporary or hereditary changes in mating type α→a in heterothallic strains of yeast Saccharomyces cerevisiae . Here, we compared yeast strains carrying mutations in DNA repair genes, mismatch repair ( pms1 ), base excision repair ( ogg1 ), and homologous recombination repair ( rad52 ), as well as mutagens causing specific DNA lesions (UV light and camptothecin). We found that double-strand breaks and UV-induced lesions have a stronger effect on the phenotype than mismatches and 8-oxoguanine. Moreover, the loss of the entire chromosome III leads to an immediate mating type switch α→a and does not prevent hybridization. We also evaluated the ability of primary DNA lesions to persist through the cell cycle by assessing the frequency of UV-induced inherited and non-inherited genetic changes in asynchronous cultures of a wild-type ( wt ) strain and in a cdc28-4 mutant arrested in the G1 phase. Our findings suggest that the phenotypic manifestation of primary DNA lesions depends on their type and the stage of the cell cycle in which it occurred. |
