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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]
The process of duplicating DNA is called DNA replication, and it takes place by first unwinding the duplex DNA molecule, starting at many locations called DNA replication origins, followed by an unzipping process that unwinds the DNA as it is being copied. However, replication does not start at all the different origins at once.
The process by which cells divide into two daughter cells is called mitosis. Once these cells are formed they enter G1, the phase in which many of the proteins needed to replicate DNA are made. After G1, the cells enter S phase during which the DNA is replicated.
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]
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.
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]