Unlike in bacteria and plasmids, DNA replication in eukaryotic cells is extremely precise, and replication initiation occurs only once in each cell cycle to ensure genomic stability. “Licensing” is the process of making the chromatin competent for DNA replication in which a collection of proteins called origin recognition complex (ORC) bind to the ori sequences. This binding is necessary for other proteins required for the onset of the S phase to bind to DNA. ORC is present throughout the cell cycle. However, other proteins required for replication initiation and chain elongation are loaded in a stepwise fashion. The onset of the S phase may be controlled by a minichromosome maintenance (MCM) complex of proteins which licenses DNA for replication, presumably by making it accessible to the DNA synthesis machinery. Several protein factors are involved in the loading process, which is regulated both positively and negatively. The level of regulator proteins, such as geminin, which blocks licensing, is also regulated by some cell cycle-dependent feedback mechanisms.
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