Molecular interactions and cellular changes during the cell cycle.
Molecular interactions and cellular changes during the cell cycle.
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DOI：
10.1016/0163-7258(83)90071-2
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发表时间：
1983
影响因子：
13.5
通讯作者：
Z. Darżynkiewicz
中科院分区：
文献类型：
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作者：
Z. Darżynkiewicz
目前形式的细胞周期概念是三十多年前由Howard和Pelc（1951）提出的。这些作者通过放射自显影研究DNA前体（32p）的结合，观察到单个细胞中的DNA合成是不连续的，并且占据了细胞生命的离散部分（S期）。有丝分裂发生在DNA复制后的一段时间后。有丝分裂和DNA复制之间有明显的时间间隔。因此，细胞周期被细分为连续的四个阶段，G~， S， G2和M. G~和G2期分别代表有丝分裂和DNA复制开始之间和DNA复制结束和有丝分裂开始之间的时间间隔。细胞周期被定义为有丝分裂的中点和随后子细胞有丝分裂的中点之间的间隔（Howard and Pelc, 1951）。关于有丝分裂的知识在半个世纪前就已经很广泛了。有丝分裂的四个阶段，即前期、中期、后期和末期，以及有丝分裂过程中细胞形态的变化是当时许多出版物的主题。然而，当时对间期知之甚少。Howard和Pelc（1951）观察到DNA复制发生在间期，这是有丝分裂之外发生对细胞繁殖至关重要的重要生化事件的第一个证据。随着时间的推移，对间期特别是G1和G2“间隙”期细胞活动的了解越来越多。最近，兴趣也集中在长时间保持静止的细胞上，但在某些情况下，它们可以通过周期进行进展，反之亦然，当循环细胞可以进入静止期。此外，细胞从周期到分化状态的转变，或通过周期的扰动进展，即发生在不平衡的细胞生长过程中，开始引起人们的注意。因此，细胞周期的主题现在涵盖了广泛的细胞代谢活动，这些活动不仅与细胞繁殖直接相关，而且还与向静止、分化或生长紊乱的过渡有关。我们目前对细胞周期的了解主要得益于四种不同技术的发展；放射自显影、延时摄影、细胞同步培养和流式细胞术。其中，放射自显影术已被广泛使用，特别是在过去的二十年。通过提供一种分析单个细胞中DNA、RNA或蛋白质前体结合的方法，并结合各种细胞同步技术，放射自显影术产生了目前对细胞周期相关现象理解的大部分基础数据。在开发了诸如测量标记有丝分裂的比例（“FLM曲线”）或使用3h和14C-TdR进行多次连续细胞标记等复杂的放射自显影方法后，可以非常详细地分析细胞周期中细胞进展的动力学。Cleaver（1967）、Baserga和Malamud（1969）、Rogers（1975）、Aherne等人（1977）和Pearse（1980）对应用于细胞周期研究的放射自显像技术直接相关的文献进行了综述。然而，这里应该提到的是
The concept of the cell cycle in its present form was introduced more than three decades ago by Howard and Pelc (1951). These authors, studying incorporation of DNA precursors (32p) by autoradiography observed that DNA synthesis in individual cells was discontinuous and occupied a discrete portion of the cell life (S phase). Mitotic division was seen to occur after a certain period of time following DNA replication. A distinct time interval between mitosis and DNA replication was also apparent. Thus, the cell cycle was subdivided into four consecutive phases, G~, S, G2, and M. The G~ and G2 phases represented the'gaps' in time between mitosis and the start of DNA replication, and between the end of DNA replication and the onset of mitosis, respectively. The cell cycle was defined as the interval between the midpoint of mitosis and the midpoint of the subsequent mitosis of the daughter cell (s)(Howard and Pelc, 1951). The knowledge about mitosis was already extensive half a century ago. Descriptions of the four stages of mitosis, ie prophase, metaphase, anaphase and telophase and changes in cellular morphology during mitosis were the subject of numerous publications at that time. However, very little was then known about interphase. The observation by Howard and Pelc (1951) that DNA replication takes place in interphase was thus the first evidence that an important biochemical event, essential for cell reproduction, occurs outside of mitosis. With time, more and more knowledge accumulated on cell activity in interphase especially during the'gap'periods in G1 and G2. More recently, interest has also focused on cells which remain quiescent for an extended period of time, but which under certain circumstances can undergo progression through the cycle, or vice versa when cycling cells can enter a period of quiescence. Also, transition of cells from the cycle to the differentiated state, or perturbed progression through the cycle, ie as occurs during unbalanced cell growth, began to attract attention. Thus, the subject of the cell cycle now covers a wide range of cell metabolic activities which are not only directly related to cell reproduction, but are also associated with transitions to quiescence, differentiation, or perturbed growth. Our present knowledge on the cell cycle benefited mostly from the development of four different techniques; autoradiography, time-lapse cinematography, cell synchronization in culture, and flow cytometry. Of these, autoradiography has been the most extensively used, especially during the past two decades. By providing a means to analyse incorporation of precursors of DNA, RNA or proteins by individual cells and, in combination with various techniques of cell synchronization, autoradiography yielded most of the data fundamental to the current understanding of the cell cycle-related phenomena. Kinetics of cell progression through the cell cycle could be analysed in great detail after development of such sophisticated autoradiographic approaches as measurements of the fraction of labeled mitoses ('FLM curves') or multiple sequential cell labelling with 3H-and 14C-TdR. The literature directly related to the autoradiographic techniques as applied to research on the cell cycle was reviewed by Cleaver (1967), Baserga and Malamud (1969), Rogers (1975), Aherne et al.(1977) and Pearse (1980). It should be mentioned here, however, that