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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.
In bacterial DNA replication, regulation focuses on the binding of the DnaA initiator protein to the DNA, with initiation of replication occurring multiple times during one cell cycle. [93] Both prokaryotic and eukaryotic DNA use ATP binding and hydrolysis to direct helicase loading and in both cases the helicase is loaded in the inactive form.
This results in a structurally functional helicase able to facilitate transcription, however it inhibits its function in unwinding DNA and DNA repair. [38] The lack of a cell's ability to repair mutations, such as those caused by sun damage, is the cause of the high cancer rate in xeroderma pigmentosa patients.
Before DNA replication can start, the pre-replicative complex assembles at origins to load helicase onto DNA. The complex assembles in late mitosis and early G1. Assembly of these pre-replicative complexes (pre-RCs) is regulated in a manner that coordinates DNA replication with the cell cycle. [6]
All eukaryotes possess many more replication origins than strictly needed during one cycle of DNA replication. [5] Redundant origins may increase the flexibility of DNA replication, allowing cells to control the rate of DNA synthesis and respond to replication stress. [5]
The minichromosome maintenance protein complex (MCM) is a DNA helicase essential for genomic DNA replication. Eukaryotic MCM consists of six gene products, Mcm2–7, which form a heterohexamer. [1] [2] As a critical protein for cell division, MCM is also the target of various checkpoint pathways, such as the S-phase entry and S-phase arrest ...
Additionally, many more replicative helicases are loaded than activated to initiate replication in a given cell cycle. The context-driven definition of replicators and selection of origins suggests a relaxed replicon model in eukaryotic systems that allows for flexibility in the DNA replication program. [23]
DNA re-replication (or simply rereplication) is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. [1] Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers . [ 2 ]