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Eukaryotes initiate DNA replication at multiple points in the chromosome, so replication forks meet and terminate at many points in the chromosome. Because eukaryotes have linear chromosomes, DNA replication is unable to reach the very end of the chromosomes. Due to this problem, DNA is lost in each replication cycle from the end of the chromosome.
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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]
During G1, cyclin D is synthesized and binds to Cdk4/6, which in turn phosphorylates retinoblastoma (Rb) protein and induces the release of the transcription factor E2F1 which is necessary for DNA replication (Liu et al., 1998). The G1/S transition is regulated by cyclin E binding to Cdk2 which phosphorylates Rb as well (Merrick and Fisher, 2011).
During DNA replication, the replisome will unwind the parental duplex DNA into a two single-stranded DNA template replication fork in a 5' to 3' direction. The leading strand is the template strand that is being replicated in the same direction as the movement of the replication fork.
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A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair. [123]