Department of Biology, Indiana University, Bloomington, Indiana, United States of America.
Department of Biochemistry and Cell Biology, the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
PLoS Genet. 2023 Apr 5;19(4):e1010707. doi: 10.1371/journal.pgen.1010707. eCollection 2023 Apr.
To prevent chromosome mis-segregation, a surveillance mechanism known as the spindle checkpoint delays the cell cycle if kinetochores are not attached to spindle microtubules, allowing the cell additional time to correct improper attachments. During spindle checkpoint activation, checkpoint proteins bind the unattached kinetochore and send a diffusible signal to inhibit the anaphase promoting complex/cyclosome (APC/C). Previous work has shown that mitotic cells with depolymerized microtubules can escape prolonged spindle checkpoint activation in a process called mitotic slippage. During slippage, spindle checkpoint proteins bind unattached kinetochores, but the cells cannot maintain the checkpoint arrest. We asked if meiotic cells had as robust of a spindle checkpoint response as mitotic cells and whether they also undergo slippage after prolonged spindle checkpoint activity. We performed a direct comparison between mitotic and meiotic budding yeast cells that signal the spindle checkpoint through two different assays. We find that the spindle checkpoint delay is shorter in meiosis I or meiosis II compared to mitosis, overcoming a checkpoint arrest approximately 150 minutes earlier in meiosis than in mitosis. In addition, cells in meiosis I escape spindle checkpoint signaling using two mechanisms, silencing the checkpoint at the kinetochore and through slippage. We propose that meiotic cells undertake developmentally-regulated mechanisms to prevent persistent spindle checkpoint activity to ensure the production of gametes.
为了防止染色体错误分离,如果动粒没有附着到纺锤体微管上,一个称为纺锤体检查点的监控机制会延迟细胞周期,从而让细胞有更多的时间来纠正不正确的连接。在纺锤体检查点激活期间,检查点蛋白与未附着的动粒结合,并发出扩散信号来抑制后期促进复合物/周期蛋白体(APC/C)。以前的工作表明,去聚合微管的有丝分裂细胞可以在一个称为有丝分裂滑溜的过程中逃脱长时间的纺锤体检查点激活。在滑溜过程中,纺锤体检查点蛋白与未附着的动粒结合,但细胞无法维持检查点阻滞。我们想知道减数分裂细胞是否像有丝分裂细胞一样具有强大的纺锤体检查点反应,以及它们是否在长时间的纺锤体检查点活动后也会发生滑溜。我们通过两种不同的检测方法对有丝分裂和减数分裂芽殖酵母细胞的纺锤体检查点反应进行了直接比较。我们发现与有丝分裂相比,减数分裂 I 或减数分裂 II 的纺锤体检查点延迟较短,减数分裂中克服检查点阻滞的时间比有丝分裂早约 150 分钟。此外,减数分裂 I 中的细胞通过两种机制逃避纺锤体检查点信号:在动粒处沉默检查点和通过滑溜。我们提出,减数分裂细胞采用发育调控机制来防止持续的纺锤体检查点活动,以确保配子的产生。