Cell cycle regulation in response to plasma membrane stress in S. cerevisae

项目摘要/摘要 酵母细胞需要快速控制其细胞周期、基因表达或蛋白质 应激反应通路激活时的稳定性。对于细胞来说， 他们的质膜和细胞壁受到各种攻击，如物理破坏， 病原体入侵和各种环境扰动。在这里，我们建议研究 质膜应激通过一种新的细胞周期抑制细胞生长和DNA复制 检查点路径。真核细胞复制它们的染色体。DNA中的错误 复制控制可能导致染色体不稳定，这是癌症的一个标志。我们的长- 学期目标是了解DNA复制控制的分子机制 压力。 在这个提案中，三个目标将检验我的假设，如果质膜损伤 通过一种新的细胞周期检查点抑制极化的细胞生长和DNA复制 路径。 Aim1将确定膜损伤如何驱动Pkc1重新定位以抑制极化细胞 成长。 AIM2将决定质膜应激信号如何激活Mpk1以抑制DNA 复制。 Aim3将确定酵母GSK-3激酶Mck1是否针对血浆上的复制蛋白 膜应力 从酵母到人类，DNA复制和膜完整性途径都被很好地保存了下来。 本研究的结果可应用于理解黄曲霉毒素的分子机制。 高等真核生物对应激的DNA复制调控。

Project Summary/Abstract Yeast cells need to rapidly control their cell cycle profile, gene expression or protein stability in response to the activation of stress response pathways. It is common for cells to suffer from various attacks to their plasma membrane and cell wall, such as physical damage, pathogen invasion and various environmental perturbations. Here we propose to study that plasma membrane stress inhibits cell growth and DNA replication through a novel cell cycle checkpoint pathway. Eukaryotic cells duplicate their chromosomes. Errors in the DNA replication control could lead to chromosome instability which is a hallmark of cancer. Our long- term goal is to understand the molecular mechanism of DNA replication control in response to stress. In this proposal, three aims will test my hypothesis if plasma membrane damage inhibits polarized cell growth and DNA replication through a novel cell cycle checkpoint pathway. Aim1 will determine how membrane damage drives Pkc1 relocation to inhibit polarized cell growth. Aim2 will determine how plasma membrane stress signal activates Mpk1 to inhibit DNA replication. Aim3 will determine if a yeast GSK-3 kinase Mck1 targets replication proteins upon plasma membrane stress DNA replication and membrane integrity pathways are well conserved from yeast to humans. The results obtained from this study can be applied to understand the molecular mechanism of DNA replication control in response to stress in higher eukaryotes.