Huang Min, Yang Chang, Nie Litong, Zhang Huimin, Zhu Dandan, Wang Chao, Park Jeong-Min, Srivastava Mrinal, Mosa Elina, Li Siting, Tang Mengfan, Feng Xu, Keast Sarah J, Stossi Fabio, Chen Junjie
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA.
Integrated Microscopy Core, Advanced Technology Cores, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Nucleic Acids Res. 2025 Jan 7;53(1). doi: 10.1093/nar/gkae1311.
Cell cycle checkpoints are the regulatory mechanisms that secure the strict order of cellular events for cell division that ensure genome integrity. It has been proposed that mitosis initiation depends on the completion of DNA replication, which must be tightly controlled to guarantee genome duplication. Contrary to these conventional hypotheses, we showed here that cells were able to enter mitosis without completion of DNA replication. Although DNA replication was not completed in cells upon depletion of MCM2, CDC45 or GINS4, these under-replicated cells progressed into mitosis, which led to cell death. These unexpected results challenge current model and suggest the absence of a cell cycle checkpoint that monitors the completion of DNA replication.
细胞周期检查点是确保细胞分裂过程中细胞事件严格顺序的调控机制，可保证基因组完整性。有人提出有丝分裂的启动取决于DNA复制的完成，而DNA复制必须受到严格控制以确保基因组复制。与这些传统假设相反，我们在此表明细胞能够在DNA复制未完成的情况下进入有丝分裂。尽管在MCM2、CDC45或GINS4缺失时细胞中的DNA复制未完成，但这些未完全复制的细胞仍进入有丝分裂，导致细胞死亡。这些意外结果挑战了当前模型，并表明不存在监测DNA复制完成情况的细胞周期检查点。
