Projects
1. Regulation of stationary phase
In response to nutrient shortage or various signals, cells cease cell division and enter quiescence. Cancer stem cells or a portion of pathogens are in the quiescent state, and their drug resistance is a major obstacle for treatment of tumors and infectious deseases. Therefore understanding the molecular basis of quiescence is clinically important. Upon consumption of essential nutrients in environments, unicellular organisms enter quiescence called stationary phase. By analyzing stationary phase of fission yeast, we have recently found that cyclin-dependent kinase (CDK) actively contributes to establishment of stationary phase (Hiraoka et al. 2023. J. Cell Sci.). In stationary phase, sizes of the nucleus and chrosomes are reduced, and chromosome fluctuation is repressed. Furthermore, CDK accumulates at the periphery of the nucleolus. These changes require CDK activity. We are curently investigating how CDK regulates the stationary phase-associated changes and what is the biological significance of the changes in fission yeast.
2. The regulatory mechanism of the meiotic kinetochore geometry
Genetic information is transmitted from parents to offspring by gametes, which are generated through a special type of cell division called meiosis. During meiosis I, homologous chromosomes segregate apart from each other. Understanding the mechanism of homologous chromosome segregation is clinically important, because meiotic chromosome missegregation is the major cause of miscarriage and Down syndrome. Homologous chromosome segregation requires fusion of kinetochores on sister chromatids, which enables attachment of sister chromatids to the same spindle pole. In fission yeast, sister kinetochore fusion depends on mating pheromone signaling (Yamamoto and Hiraoka, 2003, EMBO J) and Mrc1, which functions in the DNA replication checkpoint pathway (Hirose et al, 2011, PLoS Genet). Furthermore, sister kinetochore fusion is regulated by clustering of telomeres at the spindle pole body (a fungal centrosome) (Katsumata et al, 2016. PLoS Genet). We are currently investigating how mating pheromone signaling, Mrc1, and telomere clustering regulate sister kinetochore fusion in fission yeast
Chomosome segregation in fission yeast meiosis.
(Green: chromosomes; red: microtubules)
live1_06_cen.mp4Behavior of centromeres (centromere of chromosome II) and the SPB in fission yeast meiosis.
Wt_cen_live.mp4Clustering of telomeres during cell fusion (left below).
Green: microtubules; magenta: telomeres.
Fig2Avideo1.movClustering of telomeres by telomere-originated microtubules.
Green: microtubules; magenta: telomeres
Fig2Dvideo2.mov