Cell Cycle and Cell Division Notes

Cell Cycle and Cell Division

Learning Outcomes

• Outline the role of key processes within the cell, including cell division, and the role of metabolic pathways in the normal functioning of the cell.
• Describe specialised adaptations of cells, both prokaryotic and eukaryotic, to their environments.

Eukaryotic Cell Cycle

• Cell Division: Allows for reproduction and growth.
• Studying Cell Cycle:
  • Yeast (cdc gene): Gene controls specific steps in the eukaryotic cell cycle.
  • Xenopus
  • Mammals: Immortalized cell lines used for studies.

Cell Cycle Phases

• G0 Phase: Resting phase.
• M Phase:
  • Nuclear division; chromosomes visible.
  • Cytokinesis: True cell division; cytoplasm divides into two daughter cells.
• Interphase: Phase between divisions.

Cell Cycle Control

• Basic organization is the same in all eukaryotic cells.
• Control proteins are highly conserved.
• Cytoplasmic chemistry influences cell activity.
• Quality Assurance/Quality Control via Checkpoints.

Quality Assurance and Quality Control

• Surveillance of signals.
• Ensuring completion of previous phase before entering the next.
• Initiation and termination of chemical reactions.
• Cell cycle arrest and delay functions.
• DNA damage detection and repair.
• Programmed cell death (apoptosis).

G1 Phase

• Entry to cell cycle (Mitogenic signal).
• Microenvironmental conditions influence length.
• One DNA copy only.

Cyclin-Cdk Control

• Protein kinases drive cell cycle progression using a combination of cyclin and cyclin-dependent kinase (Cdk).
• Cyclin concentrations build up to activate Cdks.

Regulation via Phosphorylation of CDKs

• Phosphatase action (positive feedback loop).
• Late G1 phase: Cyclin D/Cdk4/6, Cyclin E/Cdk2.
• Restriction point: Commitment to S phase.

G1 Checkpoint

• G1 DNA damage checkpoint.
• p53: "Guardian of the genome"; determines entry to S phase.
  • If repair is needed, slows cell cycle; if impossible, induces apoptosis.
  • Increases expression of p21, inhibiting Cdks 2, 3, 4, and 6.
  • Downregulates Cyclin A, stopping progression into S phase.

S Phase

• One new copy of cell’s DNA is synthesized.
• Energy consumption increases.

G2 Phase and Checkpoint

• Organelle development and preparation for cytokinesis.
• Cyclin A/B/cdk1.
• DNA structure checkpoint ensures entry to Mitosis.
• Monitors for unreplicated DNA and molecular damage.
• Cell cycle arrested if repair is needed; apoptosis triggered by p53 if damage is severe.

M Phase

• Culmination of the cell cycle.
• Cyclin A/B/Cdk1.
• Metaphase checkpoint (spindle assembly/kinetochore attachment).
• Checks for misaligned chromosomes and microtubule attachment.

Summary

• Cell division in eukaryotes is an active, multiphase process (cell cycle).
• Highly conserved; includes preparation phases and cell division.
• Checkpoints are critical.
• Mitosis occupies a small portion of the cell cycle.
• Molecular quality assurance and control mechanisms prevent genome damage.

Prokaryotic Cell Cycle/Cell Division

• Called "Fission".
• Simplified due to a single, circular DNA chromosome.
• No nucleus or multiple chromosomes, so mitosis is unnecessary.
• Binary fission.
• Many archaea use a similar method of cell division.

Prokaryotes

• No nucleus, circular DNA in nucleoid area.
• Binary Fission: Chromosome replication, cell enlargement, formation of cross wall, division into daughter cells.

Cell Cycle Time Constants

• Bacterial chromosome contains a single replicon.
• Replication initiates at a single point and is bidirectional.
• C = Duration of time required for DNA replication.
• D = Minimum time between the end of DNA replication and splitting into two cells.

FtsZ-Based Cell Division Mechanism in Archaea

• Circular chromosomes with single or multiple replication origins.
• Initiated in synchrony and terminated asynchronously.
• Archaeal replication machinery homologous to eukaryotes.
• Some archaea use FtsZ-based cell division; others use a system homologous to eukaryotic ESCRT system.