A unified model for the G1/S cell cycle transition.
A unified model for the G1/S cell cycle transition.
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DOI：
10.1093/nar/gkaa1002
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发表时间：
2020-12-16
影响因子：
14.9
通讯作者：
Ramadan K
中科院分区：
文献类型：
--
作者：
Hume S;Dianov GL;Ramadan K
有效的S期进入对发育、组织修复和免疫防御至关重要。然而，过度活跃或加速的S期进入会导致复制应激、DNA损伤和肿瘤发生，因此需要严格调控。最近的范式转换和相互矛盾的报告表明有必要讨论G1/S转换文献。在此，我们回顾了最近的研究，并提出了一个统一的S阶段进入决策模型。在这个模型中，分裂原和DNA损伤信号之间的竞争在母细胞周期过程中构成了子细胞进入S期的主要控制机制。有丝分裂原和DNA损伤具有不同的感知期，从而产生S期进入的三个承诺点（CP1-3）。S期在子G1期不依赖于有丝分裂原，但对DNA损伤（如单链断裂）仍然敏感，单链断裂是最常见的威胁DNA复制的病变。为了控制CP1-3，专用枢纽整合拮抗有丝分裂和DNA损伤信号，调节化学计量周期蛋白：CDK抑制剂的比例，以超灵敏地控制CDK4/6和CDK2。G1/S细胞周期转变的统一模型结合了数十年的研究成果，为细胞周期研究提供了新的基础。
Efficient S phase entry is essential for development, tissue repair, and immune defences. However, hyperactive or expedited S phase entry causes replication stress, DNA damage and oncogenesis, highlighting the need for strict regulation. Recent paradigm shifts and conflicting reports demonstrate the requirement for a discussion of the G1/S transition literature. Here, we review the recent studies, and propose a unified model for the S phase entry decision. In this model, competition between mitogen and DNA damage signalling over the course of the mother cell cycle constitutes the predominant control mechanism for S phase entry of daughter cells. Mitogens and DNA damage have distinct sensing periods, giving rise to three Commitment Points for S phase entry (CP1-3). S phase entry is mitogen-independent in the daughter G1 phase, but remains sensitive to DNA damage, such as single strand breaks, the most frequently-occurring lesions that uniquely threaten DNA replication. To control CP1-3, dedicated hubs integrate the antagonistic mitogenic and DNA damage signals, regulating the stoichiometric cyclin: CDK inhibitor ratio for ultrasensitive control of CDK4/6 and CDK2. This unified model for the G1/S cell cycle transition combines the findings of decades of study, and provides an updated foundation for cell cycle research.
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影响因子：
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