Cell Cycle Overview

Study Notes

The cell cycle is a series of events leading to cell duplication and division.
In bacteria, cell growth and DNA replication occur throughout most of the cycle, and duplicated chromosomes are distributed to daughter cells with the plasma membrane.
Eukaryotic cell cycles are more complex. DNA synthesis occurs during only one phase, and replicated chromosomes are distributed to daughter nuclei by complex events before division.
Eukaryotic cell cycles consist of 4 coordinated processes: cell growth, DNA replication, distribution of duplicated chromosomes to daughter cells, and cell division.
Typical eukaryotic cell cycles (like human cells in culture) take about 24 hours.
Mitosis and cytokinesis typically take about an hour, meaning interphase (the period between cell divisions) takes up about 95% of the cell cycle.
Cell cycle duration varies greatly. For example, budding yeasts can complete the entire cell cycle in 90 minutes.

Progression through the cell cycle is regulated by extracellular signals from the environment and internal signals that control and monitor different processes.
Cyclin-dependent kinases (Cdks). Regulation of cell processes at checkpoints are controlled by the activation of Cdk subunits.
Animal cell cycle progression through the G1 restriction point is controlled by Cdk4/Cdk6 with D-type cyclins and Cdk2/cyclin E complexes function in later steps.
Cdk1/ cyclin A regulates progression to G2. Cdk1/cyclin B complexes are responsible for driving the G2 to M phases.
Other protein kinase steps regulate the cell cycle.

Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle ensuring proper progression.
Checkpoints detect DNA damage from external agents, DNA replication issues, and chromosome attachment problems.

DNA replication is restricted to once per cell cycle.
MCM proteins bind to origins of replication and are required for DNA replication initiation in the G1 phase, but these proteins are displaced, preventing later replication until the cycle repeats.

Mitosis stages. Mitosis involves several steps including prophase, prometaphase, metaphase, anaphase, and telophase.
Cdk1/cyclin B regulates progression to metaphase by altering proteins and inducing numerous nuclear and cytoplasmic changes.
Spindle assembly checkpoint and progression to anaphase.
Cytokinesis.

By default, the protein E2F is masked by Rb. In the G1/S checkpoint , Cdk4/Cdk6 along with cyclin D phosphorylates Rb. this phosphorylation makes Rb inactivate allowing for the production of replication enzymes.
Growth factors can stimulate cell cycle progression by reducing the levels of p27, which then increases the activity of Cdk2/cyclin E complexes. This is part of how factors determine when to replicate

ATMs and ATRs recognize damaged DNA and activate further steps.
Activated CHK enzymes then phosphorylate and inhibit specific proteins, stopping the cycle.
P53 is a key tumor suppressor protein, involved in responding to DNA damage and initiating cell cycle arrest at the G1 checkpoint, which includes regulating the activity of specific complexes, and leading to programmed cell death.