Nuclear morphology checkpoint: analysis of the nuclear division arrest caused

2015 Fiscal Year Final Research Report

• Project/Area Number: 25660055
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied microbiology
• Research Institution: Kyoto University
• Principal Investigator: Yoshiharu Inoue 京都大学, (連合)農学研究科(研究院), 准教授 (70203263)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: メチルグリオキサール / 酵母 / 核分裂 / ホスファチジルイノシトール3.5-ビスリン酸 / 核形態 / 液胞 / DNA損傷チェックポイント

Outline of Final Research Achievements

Methylglyoxal (MG) is derived from glycolysis. We found that MG inhibited the nuclear division in yeast. MG treatment changed yeast vacuole to a single enlarged shape, which altered the nuclear morphology to one with a central depression aligned with the mother-bud axis, which we referred to as a “jellybean-like shape” nucleus. We showed that the levels of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) were increased with MG treatment. PI(3,5)P2 levels did not increase in mutants defective in Fig4 or Vac14 following treatment with MG, and these mutants did not show the MG-induced nuclear division arrest. Atg18, a PI(3,5)P2-binding protein, was enriched on the vacuolar membrane with MG treatment, and the deletion of ATG18 suppressed the inhibitory effect of MG on nuclear division. We showed that MG activated the DNA damage checkpoint. Degradation of cohesin was inhibited in the presence of MG, which indicated that sister chromatid segregation was stalled.

Free Research Field

分子細胞生物学