Cell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Laboratory of Yeast Genetics and Cell Biology, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
J Cell Sci. 2022 Jun 15;135(12). doi: 10.1242/jcs.259626. Epub 2022 Jun 21.
The eukaryotic cell cycle is driven by the activity of cyclin-dependent kinases (CDKs). CDK activity rises over 50-fold during the cell cycle, from a low level in G1 to a high level in mitosis. However, it is not known whether the entire range of CDK activity is necessary for cell cycle progression, or whether cells can tolerate a reduction in CDK activity level. Here, in fission yeast, we show that sublethal CDK inhibition lengthens the time cells spend in mitosis but does not cause misordering of mitotic events. Maximum attainable CDK activity exceeds the amount necessary for mitosis, and thus forms a CDK activity buffer between sufficient and maximal possible CDK activities. This CDK activity buffer is needed for mitotic completion when CDK activity is compromised, and CDK inhibition only becomes lethal to cells when this buffer is exhausted. Finally, we explore what factors influence this CDK activity buffer, and find that it is influenced by CDK-counteracting phosphatases. Therefore, maximum attainable CDK activity is not necessary for mitosis but provides robustness to CDK activity reduction to ensure mitotic completion.
真核细胞周期由细胞周期蛋白依赖性激酶 (CDK) 的活性驱动。在细胞周期中，CDK 活性升高了 50 多倍，从 G1 期的低水平升高到有丝分裂期的高水平。然而，目前尚不清楚整个 CDK 活性范围是否对细胞周期进程是必需的，或者细胞是否可以耐受 CDK 活性水平的降低。在这里，在裂殖酵母中，我们表明亚致死性 CDK 抑制会延长细胞在有丝分裂中花费的时间，但不会导致有丝分裂事件的混乱。最大可达的 CDK 活性超过了有丝分裂所需的量，因此在足够和最大可能的 CDK 活性之间形成了 CDK 活性缓冲。当 CDK 活性受到影响时，这个 CDK 活性缓冲对于有丝分裂的完成是必需的，只有当这个缓冲耗尽时，CDK 抑制才会对细胞产生致命影响。最后，我们探讨了哪些因素会影响这个 CDK 活性缓冲，发现它受 CDK 拮抗磷酸酶的影响。因此，最大可达的 CDK 活性对有丝分裂不是必需的，但它为 CDK 活性的降低提供了稳健性，以确保有丝分裂的完成。
