Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Inheritance of the genome stably and correctly is one of the most fundamental life activities of all living things. When DNA is damaged for some reason, cells arrest the cell cycle until it is repaired. If DNA damages are not repaired correctly, it will be fixed in the DNA as a mutation and the wrong genetic information will be passed on to the next generation. Besides the external factors such as ultraviolet rays, it is also known that DNA damages are provoked by some metabolites produced during intracellular energy metabolism that show genetic toxicity. For example, methylglyoxal (MG), which is generated from an intermediate of triosephosphate isomerase reaction, which is one of glycolytic enzymes, forms an adduct with a guanine residue in DNA.
We are studying the physiological function of MG using the budding yeast (Saccharomyces cerevisiae) as a model organism. It has been reported that high concentrations of MG gave lethal effect on all organisms including yeast. We found that sublethal concentrations of MG inhibited nuclear division and transformed the nuclear morphology from spheres to a flattened “jellybeans-like shape” in yeast. The nucleus of eukaryotes is usually spherical. Unlike higher eukaryotes, budding yeast performs closed mitosis in which the nuclear envelope does not disappear during nuclear division. Therefore, the nuclei of anaphase, where nuclear division occurs, are stretched along the growth axis between mother cells and daughter cells, but are basically spherical in other cell cycles. We found that treatment of yeast with MG induced the phosphorylation of Tyr19 of the cyclin-dependent kinase Cdc28 (G2/M arrest), and the nucleus resides in the mother cell near the bud neck (between mother and daughter cells). Furthermore, the nuclear morphology changed from a globate shape to one with a central depression aligned with the mother-bud axis, which we refer as a “jellybean-like shape” of the nucleus, following treatment with MG, and the nucleus remains in the mother cell even though the daughter cell is large enough to accept the nucleus. In this symposium, I would like to introduce the machinery involved in the MG-induced inhibition of nuclear division and predicted mechanism underlying.
