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Cell Cycle Regulation and DNA Replication

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Exploring the mechanisms of cell cycle regulation, this overview highlights the roles of cyclin-dependent kinases (CDKs), pre-replication complexes (pre-RCs), and checkpoint proteins in DNA replication. It delves into the prevention of DNA re-replication through the dynamics of Cdt1 and geminin, the importance of cell cycle checkpoints, particularly the G1/S transition, and the function of replication checkpoint proteins like ATR and ATM in maintaining genomic integrity. Additionally, it discusses the involvement of histone chaperones in chromatin assembly during DNA replication and contrasts prokaryotic and eukaryotic replication processes.

Cell Cycle Regulation by Cyclin-Dependent Kinases and Pre-Replication Complexes

The cell cycle is an essential and highly regulated sequence of events in a cell that leads to DNA replication and cell division. Cyclin-dependent kinases (CDKs) are pivotal in controlling the cell cycle's progression. During the G1 phase, CDK activity is minimal, allowing the assembly of pre-replication complexes (pre-RCs) on the DNA, which are necessary for the initiation of DNA replication. As the cell transitions from G1 to S phase, CDK activity increases, triggering the start of DNA replication and simultaneously inhibiting the formation of new pre-RCs. This regulation ensures that each segment of DNA is replicated only once per cell cycle, thus preserving genomic stability.
Eukaryotic cell in mitotic metaphase with chromosomes aligned to the equatorial plane, highlighted centromeres and connected spindle fibers.

Prevention of DNA Re-replication by Geminin and Cdt1 Dynamics

Cells employ a safeguard mechanism to prevent DNA re-replication, involving regulatory proteins such as Cdt1 and geminin. Cdt1 is crucial for the recruitment of the minichromosome maintenance (MCM) complex to DNA, a step necessary for replication initiation. Its activity is tightly controlled by proteolysis and by inhibition through geminin binding. Geminin accumulates during the S phase to inhibit Cdt1 and is degraded during the metaphase-anaphase transition, likely via ubiquitination by the anaphase-promoting complex/cyclosome (APC/C). This precise temporal regulation of Cdt1 and geminin is vital for ensuring that DNA replication occurs once per cell cycle.

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00

Cell cycle phases for DNA replication

G1 phase: pre-RC assembly, low CDK; S phase: DNA replication, high CDK, pre-RC formation inhibited.

01

Purpose of pre-replication complexes

Pre-RCs are necessary for initiating DNA replication during the cell cycle.

02

Mechanism to ensure DNA replicates once per cycle

Increased CDK activity in S phase inhibits new pre-RCs, ensuring single DNA replication event.

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