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During S-phase, the cell converts pre-RCs into active replication forks to initiate DNA replication. [4] This process depends on the kinase activity of Cdc7 and various S-phase CDKs, both of which are upregulated upon S-phase entry. [4] Activation of the pre-RC is a closely regulated and highly sequential process.
The eukaryotic cell cycle consists of four distinct phases: G 1 phase, S phase (synthesis), G 2 phase (collectively known as interphase) and M phase (mitosis and cytokinesis). M phase is itself composed of two tightly coupled processes: mitosis, in which the cell's nucleus divides, and cytokinesis, in which the cell's cytoplasm and cell membrane divides forming two daughter cells.
Mitosis is preceded by the S phase of interphase (during which DNA replication occurs) and is followed by telophase and cytokinesis, which divide the cytoplasm, organelles, and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. [2]
Figure 1: Schematic of the cell cycle. outer ring: I = Interphase, M = Mitosis; inner ring: M = Mitosis, G 1 = Gap 1, G 2 = Gap 2, S = Synthesis; not in ring: G 0 = Gap 0/Resting. Replication timing refers to the order in which segments of DNA along the length of a chromosome are duplicated.
At the G1/S checkpoint, p53 acts to ensure that the cell is ready for DNA replication, while at the G2/M checkpoint p53 acts to ensure that the cells have properly duplicated their content before entering mitosis. [40] Specifically, when DNA damage is present, ATM and ATR kinases are activated, activating various checkpoint kinases. [41]
Mitotic DNA synthesis (MiDAS) is a process of irregular DNA replication where DNA synthesis, naturally occurring in the S phase, takes place in the M phase of the cell cycle. Mitotic DNA synthesis is known to occur when cells are experiencing stress related to DNA replication . [ 151 ]
Within eukaryotes, DNA replication is controlled within the context of the cell cycle. As the cell grows and divides, it progresses through stages in the cell cycle; DNA replication takes place during the S phase (synthesis phase). The progress of the eukaryotic cell through the cycle is controlled by cell cycle checkpoints.
The cell cycle is a series of complex, ordered, sequential events that control how a single cell divides into two cells, and involves several different phases. The phases include the G1 and G2 phases, DNA replication or S phase, and the actual process of cell division, mitosis or M phase. [1]