34.3
细胞周期控制系统
细胞周期是一组有组织的事件，导致细胞分裂成两个子细胞，每个子细胞都包含与亲代细胞相同的染色体。 细胞周期导致从单细胞受精卵形成整个生物体。 此外，细胞分裂还在成年多细胞真核生物的组织更新或修复中发挥作用。 例如，在骨髓中，干细胞分裂形成新的血细胞。 尽管细胞分裂对于多种功能至关重要，但在缺乏控制机制…
细胞周期包括细胞内物质的复制，随后分裂为两个子细胞。
细胞内容物（尤其是DNA）的复制过程极为关键，该过程中的任何错误都可能导致癌症等疾病。
那么细胞如何在分裂过程中防止出现任何错误呢？
细胞周期调控系统包含多种调节蛋白，可在不同检查点停止细胞周期进程。
在每个检查点，调节蛋白会阻止各步骤的启动，直到前期阶段完成且所有错误均已得到纠正。
通常，细胞周期调控系统在 G1、G2 和 M 期存在三个关键的检查点。
在G1检查点，调控蛋白会检测细胞是否已达到关键大小，以及DNA是否无错误。同时还会检测是否存在足够的营养物质和生长因子以启动DNA合成。
此时，如果细胞未接收到必要的信号，便会进入一种称为 G0 期的静息状态，直到所有条件满足为止。
通过G1检查点的细胞将进入合成期（S期），此时DNA进行复制。
此后，细胞在G2期遇到第二个检查点，此时调控蛋白会检查DNA是否存在错误，以及细胞是否具有合适的大小以进入有丝分裂期（M期）。
在有丝分裂过程中，调控系统会检测染色体是否已连接到纺锤体并准确排列，以确保细胞周期能够继续进行细胞分裂。如果在任何阶段调控蛋白检测到不可修复的损伤，则会引发细胞死亡。一类关键的调控蛋白是依赖细胞周期蛋白的蛋白激酶（cyclin-dependent protein kinases，CDK）。CDK 与细胞周期蛋白结合形成复合物，其活性会影响直接参与细胞生长和 DNA 合成的蛋白质。
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Q1: What mechanisms control progression through the cell cycle?
The cell cycle is regulated by a complex system of proteins, primarily cyclins and cyclin-dependent kinases (CDKs), which act as molecular switches. These regulatory proteins control when cells enter different phases, ensuring DNA replication occurs accurately before division. Checkpoint mechanisms monitor cell conditions and halt progression if problems are detected, maintaining cellular integrity.
Q2: How do checkpoints prevent cells from dividing with damaged DNA?
Cell cycle checkpoints are control points that assess whether conditions are appropriate for progression. They monitor DNA integrity, chromosome attachment, and nutrient availability. If damage is detected, checkpoint proteins halt the cycle, allowing time for repair or triggering cell death if damage is irreparable, preventing transmission of mutations to daughter cells.
Q3: What role do cyclins and cyclin-dependent kinases play in cell division?
Cyclins are regulatory proteins whose levels fluctuate throughout the cell cycle, while cyclin-dependent kinases are enzymes activated only when bound to cyclins. Together, they phosphorylate target proteins that drive cell cycle transitions. Different cyclin-CDK complexes control specific phases, ensuring events occur in the correct sequence and timing.
Q4: Why is the G1 checkpoint critical for cell cycle control?
The G1 checkpoint, also called the restriction point, determines whether a cell commits to DNA replication. Cells assess nutrient availability, growth signals, and DNA damage at this stage. Once cells pass this checkpoint and enter S phase, they are committed to completing the cell cycle regardless of external conditions.
Q5: How do external signals influence cell cycle progression?
Growth factors and hormones bind to cell surface receptors, triggering signal transduction pathways that activate cyclin-CDK complexes. These external signals promote progression through G1 phase and entry into S phase. Conversely, stress signals or nutrient deprivation can inhibit these pathways, halting cell cycle progression.
Q6: What happens when cell cycle control mechanisms fail?
Failure of cell cycle control can lead to uncontrolled cell division and cancer development. Mutations in genes encoding cyclins, CDKs, or checkpoint proteins can disable regulatory mechanisms. Cells may bypass checkpoints, accumulate DNA damage, and divide inappropriately, contributing to tumor formation and disease progression.