酵母细胞中枢细胞作为组织中心,促进Polo激酶介导的适应性,以对持续的DNA损伤进行治疗
Laurence Langlois-Lemay1, Damien D'Amours1
1Ottawa Institute of Systems Biology, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
概括
波罗样类激酶 (PLKs) 通过招募螺旋杆体 (SPBs) 来帮助细胞适应DNA损伤. SPBs协调这个过程,使细胞能够绕过细胞循环停止并适应DNA损伤.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 细胞循环停止和适应DNA损伤是由波罗样酶 (PLKs) 调节的.
- 适应过程中DNA损伤检查点沉默的机制涉及到Cdc5 PLK向微管组织中心 (MTOC) 的丰富.
研究的目的:
- 研究螺旋杆体 (SPB) 作为超分子组织中心在协调Cdc5 PLK招募和DNA损伤适应过程中的信号传递中的作用.
- 确定关键的SPB组件和参与该过程的下游影响因素.
主要方法:
- 研究了持续DNA损伤的酵母细胞中Cdc5 PLK对SPB的招募.
- 确定了对Cdc5招募至关重要的SPB组件 (Nud1, Spc110, Spc72).
- 通过Cdc5.5分析了SPB子单位 (Cnm67,Mps3) 的酸化.
- 评估了这些酸化事件对细胞周期绕过和适应的要求.
主要成果:
- 在DNA损伤适应过程中,SPB积极协调Cdc5的招募和信号.
- 在DNA受损的情况下,Nud1,Spc110和Spc72是Cdc5招募到SPB的关键.
- Cdc5酸化了SPB子单元Cnm67和Mps3,这对于绕过细胞循环停止至关重要.
- 这种适应反应是特定的,而不是由于一般的MTOC失活.
结论:
- SPBs的功能是作为超分子组织中心招募和激活PLKs以适应DNA损伤.
- 中心细胞作为平台协调PLK招募和基质选择在DNA损伤反应 (DDR).
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