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裂殖酵母 Wee1 对于稳定的动粒-微管连接是必需的。

Fission yeast Wee1 is required for stable kinetochore-microtubule attachment.

机构信息

Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.

Kobe Frontier Research Center, Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe 651-2492, Japan.

出版信息

Open Biol. 2024 Jan;14(1):230379. doi: 10.1098/rsob.230379. Epub 2024 Jan 3.

DOI:10.1098/rsob.230379
PMID:38166399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10762435/
Abstract

Wee1 is a cell cycle regulator that phosphorylates Cdk1/Cdc2 and inhibits G2/M transition. Loss of Wee1 in fission yeast results in an early onset of mitosis. Interestingly, we found that cells lacking Wee1 require the functional spindle checkpoint for their viability. Genetic analysis indicated that the requirement is not attributable to the early onset of mitosis. Live-cell imaging revealed that some kinetochores are not attached or bioriented in the mutant. Furthermore, Mad2, a component of the spindle checkpoint known to recognize unattached kinetochores, accumulates in the vicinity of the spindle, representing activation of the spindle checkpoint in the mutant. It appears that the mutant cannot maintain stable kinetochore-microtubule attachment, and relies on the delay imposed by the spindle checkpoint for establishing biorientation of kinetochores. This study revealed a role of Wee1 in ensuring accurate segregation of chromosomes during mitosis, and thus provided a basis for a new principle of cancer treatment with Wee1 inhibitors.

摘要

Wee1 是一种细胞周期调节剂，可磷酸化 Cdk1/Cdc2 并抑制 G2/M 期转换。裂殖酵母中 Wee1 的缺失会导致有丝分裂的早期发生。有趣的是，我们发现缺乏 Wee1 的细胞需要有功能的纺锤体检查点才能存活。遗传分析表明，这种需求不是由于有丝分裂的早期发生。活细胞成像显示，一些动粒在 突变体中未附着或不对向。此外，Mad2 是纺锤体检查点的一个组成部分，已知其可识别未附着的动粒，在纺锤体附近积累，代表纺锤体检查点在突变体中的激活。似乎 突变体不能维持稳定的动粒-微管附着，并且依赖纺锤体检查点施加的延迟来建立动粒的对向性。这项研究揭示了 Wee1 在确保有丝分裂过程中染色体准确分离中的作用，为使用 Wee1 抑制剂治疗癌症提供了新的原则基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/e3237b421e29/rsob230379f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/9df38f8e3927/rsob230379f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/c487a6886383/rsob230379f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/88a4a3ceefdd/rsob230379f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/56b28ed7aa6f/rsob230379f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/e3237b421e29/rsob230379f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/9df38f8e3927/rsob230379f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/c487a6886383/rsob230379f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/88a4a3ceefdd/rsob230379f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/56b28ed7aa6f/rsob230379f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f19a/10762435/e3237b421e29/rsob230379f05.jpg

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Differential properties of mitosis-associated events following CHK1 and WEE1 inhibitor treatments in human tongue carcinoma cells.人舌癌细胞中 CHK1 和 WEE1 抑制剂处理后与有丝分裂相关事件的差异特性。
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