关键词: Closed mitosis Cut Lipid metabolism Mitotic catastrophe Nitrogen availability TOR

Mesh : Schizosaccharomyces / metabolism genetics Mitosis Nitrogen / metabolism Schizosaccharomyces pombe Proteins / metabolism genetics Lipid Metabolism Mutation / genetics

来  源:   DOI:10.1242/jcs.262196

Abstract:
Mitosis is a crucial stage in the cell cycle, controlled by a vast network of regulators responding to multiple internal and external factors. The fission yeast Schizosaccharomyces pombe demonstrates catastrophic mitotic phenotypes due to mutations or drug treatments. One of the factors provoking catastrophic mitosis is a disturbed lipid metabolism, resulting from, for example, mutations in the acetyl-CoA/biotin carboxylase (cut6), fatty acid synthase (fas2, also known as lsd1) or transcriptional regulator of lipid metabolism (cbf11) genes, as well as treatment with inhibitors of fatty acid synthesis. It has been previously shown that mitotic fidelity in lipid metabolism mutants can be partially rescued by ammonium chloride supplementation. In this study, we demonstrate that mitotic fidelity can be improved by multiple nitrogen sources. Moreover, this improvement is not limited to lipid metabolism disturbances but also applies to a number of unrelated mitotic mutants. Interestingly, the partial rescue is not achieved by restoring the lipid metabolism state, but rather indirectly. Our results highlight a novel role for nitrogen availability in mitotic fidelity.
摘要:
有丝分裂是细胞周期的关键阶段,由庞大的监管机构网络控制,以应对多种内部和外部因素。裂殖酵母裂殖酵母可能由于突变或药物治疗而表现出灾难性的有丝分裂表型。引起灾难性有丝分裂的因素之一是脂质代谢紊乱,由于例如乙酰辅酶A/生物素羧化酶(cut6)中的突变,在脂肪酸合成酶(fas2/lsd1)中,或在脂质代谢(cbf11)基因的转录调节因子中,以及用脂肪酸合成抑制剂治疗。先前表明,氯化铵可以部分挽救脂质代谢突变体中的有丝分裂保真度。在这项研究中,我们证明了多种氮源可以改善有丝分裂的保真度。此外,这种改善不仅限于脂质代谢紊乱,还适用于许多无关的有丝分裂突变体。有趣的是,部分挽救不是通过恢复脂质代谢状态来实现的,而是间接的。我们的结果强调了氮利用率在有丝分裂保真度中的新作用。
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