Describe the various steps involved in the initiation of replication in eukaryot

Question

Describe the various steps involved in the initiation of replication in eukaryotes. What proteins are involved in each of the steps, and when in the cell cycle does each of them occur? How does their temporal segregation contribute to the limitation of origin firing to at most once per cell cycle? Describe the various steps involved in the initiation of replication in eukaryotes. What proteins are involved in each of the steps, and when in the cell cycle does each of them occur? How does their temporal segregation contribute to the limitation of origin firing to at most once per cell cycle? Describe the various steps involved in the initiation of replication in eukaryotes. What proteins are involved in each of the steps, and when in the cell cycle does each of them occur? How does their temporal segregation contribute to the limitation of origin firing to at most once per cell cycle?

Explanation / Answer

Eukaryotic DNA replication is regulated to ensure all chromosomes replicate once and only once per cell cycle. Replication begins at many origins scattered along each chromosome. Except for budding yeast, origins are not defined DNA sequences and probably are inherited by epigenetic mechanisms. Initiation at origins occurs throughout the S phase according to a temporal program that is important in regulating gene expression during development. Most replication proteins are conserved in evolution in eukaryotes and archaea, but not in bacteria. However, the mechanism of initiation is conserved and consists of origin recognition, assembly of pre-replication (pre-RC) initiative complexes, helicase activation, and replisome loading. Cell cycle regulation by protein phosphorylation ensures that pre-RC assembly can only occur in G1 phase, whereas helicase activation and loading can only occur in S phase. Checkpoint regulation maintains high fidelity by stabilizing replication forks and preventing cell cycle progression during replication stress or damage.

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