Chapter 10 pt. 2 (March 19, 2025)

Cell Cycle Overview

The cell cycle consists of various phases: G1 (Gap 1), S (Synthesis), G2 (Gap 2), and M (Mitosis).

Events must occur in sequence for proper cell cycle progression.

The presence of an external control system, influenced by signals from the environment, governs the timing of these phases.

HeLa Cells Background

HeLa cells, taken from Henrietta Lacks in the 1950s without consent, continue to live and divide to this day.

These cells have greatly contributed to medical research, despite the unethical practices of their collection.

Cell Cycle Control Mechanisms

Significance of External Signals:

• Experiments showed that fusion of cells in different phases can influence each other's cycle—demonstrating the existence of external factors triggering cell cycle progression.
• Chemical signals or growth factors from neighboring cells can prompt cells to divide or wait based on environmental cues.

Cell Cycle Checkpoints

Three important checkpoints:

1. G1 Checkpoint

• Assesses if conditions are favorable for division (growth signals, DNA integrity).

1. G2 Checkpoint

• Ensures DNA has been accurately replicated; checks for damage before entering mitosis.

1. M Checkpoint

• Confirms all chromosomes are aligned correctly and attached to spindle fibers.

Role of p53 Protein

Acts as a guardian of the genome by halting the cycle upon detection of DNA damage.

When activated, it triggers repair mechanisms or initiates apoptosis (cell suicide) if damage is irreparable, protecting neighboring cells.

Cyclin-Dependent Kinases (CDKs)

Key players in cell cycle regulation.

CDKs are activated by binding to cyclins, allowing them to phosphorylate target proteins necessary for cell cycle transitions.

• Cyclins fluctuate in concentration throughout the cycle, whereas CDKs remain constant.
• Cyclin-CDK complexes are critical for driving the cell through each checkpoint.

Types of Cyclin-Dependent Kinases

G1/S CDK: Activates genes for entry into S phase.

S CDK: Initiates DNA replication.

M CDK: Drives the cell through mitosis.

Metaphase to Anaphase Transition

Triggered by the degradation of cyclins, regulating the progression of cell division.

The Anaphase Promoting Complex (APC) tags cyclins for destruction, leading to the separation of sister chromatids.

Environmental Signals

Cells require external signals to decide to divide; this is closely linked to their surrounding conditions, often governed by secreted growth factors from neighboring cells.

Example: Platelet-derived growth factor stimulates cell division post-injury by promoting localized proliferation.

Conclusion

The control of the cell cycle is crucial in cancer biology; understanding the mechanisms allows for potential therapies targeting specific mutations or signals involved in tumor growth.

Redundant control mechanisms ensure that malignant divisions do not occur capriciously, but rather in a regulated manner, albeit many cancers exploit these controls to progress unchecked.