Department of Biochemistry, Oxford University, Oxford OX1 3QU, UK.
Department of Biological Sciences, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061.
Mol Biol Cell. 2024 Jun 1;35(6):ar77. doi: 10.1091/mbc.E24-03-0142. Epub 2024 Apr 10.
In favorable conditions, eukaryotic cells proceed irreversibly through the cell division cycle (G1-S-G2-M) in order to produce two daughter cells with the same number and identity of chromosomes of their progenitor. The integrity of this process is maintained by "checkpoints" that hold a cell at particular transition points of the cycle until all requisite events are completed. The crucial functions of these checkpoints seem to depend on irreversible bistability of the underlying checkpoint control systems. Bistability of cell cycle transitions has been confirmed experimentally in frog egg extracts, budding yeast cells and mammalian cells. For fission yeast cells, a recent paper by Patterson (2021) provides experimental evidence for an abrupt transition from G2 phase into mitosis, and we show that these data are consistent with a stochastic model of a bistable switch governing the G2/M checkpoint. Interestingly, our model suggests that their experimental data could also be explained by a reversible/sigmoidal switch, and stochastic simulations confirm this supposition. We propose a simple modification of their experimental protocol that could provide convincing evidence for (or against) bistability of the G2/M transition in fission yeast.
在有利条件下,真核细胞不可逆地通过细胞分裂周期(G1-S-G2-M),以便产生两个具有与其亲代相同数量和染色体身份的子细胞。这个过程的完整性由“检查点”维持,这些检查点将细胞保持在周期的特定过渡点,直到完成所有必需的事件。这些检查点的关键功能似乎取决于潜在的检查点控制系统的不可逆双稳态。在青蛙卵提取物、出芽酵母细胞和哺乳动物细胞中,已经通过实验证实了细胞周期转换的双稳态。对于裂殖酵母细胞,Patterson (2021)的一篇最新论文提供了实验证据,证明了从 G2 期到有丝分裂的突然转变,我们表明这些数据与控制 G2/M 检查点的双稳态开关的随机模型一致。有趣的是,我们的模型表明,他们的实验数据也可以用可逆/ 双曲线开关来解释,随机模拟证实了这一假设。我们提出了对他们的实验方案的一个简单修改,这可能为裂殖酵母 G2/M 转变的双稳态提供令人信服的证据(或反对)。