Cell Cycle Notes

Definition and Basics of the Cell Cycle

• The cell cycle is the series of events that a cell goes through from one division to the next.
• It includes cell growth, DNA replication, and cell division.
• This process ensures new cells have the correct genetic material.
• Occurs in both prokaryotic and eukaryotic cells but differs in complexity.

Cell Cycle in Prokaryotes (Binary Fission)

• Prokaryotes reproduce through binary fission, a simple cell division process.
• Divided into three phases:
  • Replication phase (R-phase or C-period):
    • The bacterial genome is copied.
    • In Escherichia coli, it takes about 40 minutes.
  • Division phase (D-phase or D-period):
    • Daughter chromosomes and cell parts separate into new cells.
    • FtsZ protein forms a Z-ring at the cell's midpoint to start cell division.
  • Interval phase (I-phase or B-period):
    • Resting time between cell division and the next replication cycle.

Role of FtsZ Protein in Prokaryotic Division

• FtsZ protein is essential for prokaryotic cell division (cytokinesis).
• It polymerizes to form a ring that marks the division site and helps form the septum.

Cell Cycle in Eukaryotes

• Eukaryotic cell cycle is more complex, with four main phases:
  • G1 phase (Gap 1):
    • Cell grows and makes proteins after mitosis.
    • Regulatory checks occur.
    • Lasts about 11 hours in human cells.
  • S phase (Synthesis):
    • DNA is replicated, doubling the chromosome number.
    • Centrioles also duplicate.
    • Lasts about 8 hours in human cells.
  • G2 phase (Gap 2):
    • Cell prepares for mitosis after DNA synthesis.
    • Checks for DNA integrity and readiness for division.
    • Lasts about 4 hours.
  • M phase (Mitosis):
    • Cell divides (mitosis and cytokinesis).
    • Relatively short, about 1 hour.

GO Phase - Cell Cycle Exit

• Many cells enter GO, a resting phase where they don't divide.
• This can be temporary or permanent.
• Quiescent cells can re-enter the cycle with the right signals.
• Senescent cells (aging cells) are permanently arrested.

Variability in Cell Division Capabilities Across Cell Types

• Mature red blood cells (RBCs) and neurons can't divide.
• Differentiated cells, like liver cells, can divide under certain conditions.
• Stem cells and epithelial cells divide frequently.

Key Conclusions

• The Cell Cycle Is Fundamental to Cellular Reproduction and Growth
  • The cell cycle controls cell reproduction by ensuring DNA is copied and distributed correctly.
  • Critical for growth, tissue maintenance, and repair.
• Binary Fission Is the Efficient and Streamlined Prokaryotic Cell Cycle
  • Prokaryotic cells have a simple cycle of DNA replication followed by cell division.
  • Uses proteins like FtsZ, not found in eukaryotes.
• Eukaryotic Cell Cycle Control Is More Elaborate
  • Eukaryotes have interphase (G1, S, G2) before mitosis, allowing control and checkpoints.
  • Ensures DNA and cell components are ready before division.
• Quiescence and Senescence Represent Critical Regulatory States
  • Cells can exit the cycle into GO for differentiation and longevity of non-dividing cells.
  • Balances cell division with specialized functions.
• Cell Division Capacity Varies Widely Among Cell Types
  • Different cell types have different division potentials, controlled by development and external signals.
  • Controls cell cycle re-entry and tissue regeneration.

Important Details

• Detailed Timing of Cell Cycle Phases in Human Cells
  • Rapidly dividing human cells take about 24 hours for a full cycle:
  • G1 phase: ~11 hours
  • S phase: ~8 hours
  • G2 phase: ~4 hours
  • M phase: ~1 hour
• Replication Phase in Prokaryotes Has Equivalent Terminology
  • R-phase is the same as C-period.
  • Division into R, D, and I phases shows how replication and division are linked but separate in time.
• FtsZ and Septum Formation
  • FtsZ forms a ring as an early step in separating bacterial cells.
• Regulatory Checks in G1 and G2 Phases in Eukaryotes
  • Cells check conditions, DNA integrity, and readiness to proceed during G1 and G2.
  • Checkpoints prevent genomic instability and diseases like cancer.
• GO Phase Subtypes and Functional Implications
  • Quiescent GO cells are active but don't replicate; they can re-enter the cycle (e.g., liver regeneration).
  • Senescent cells permanently exit the cycle, contributing to aging.
• Examples of Cell Cycle Competency in Various Cell Types
  • Hematopoietic stem cells and epithelial cells have high division rates for renewal.
  • Mature neurons and RBCs are terminally differentiated and can't re-enter the cycle.
• References Supporting Key Concepts
  • Wang & Levin (2009) explain bacterial metabolism and cell cycle connections.
  • Margolin (2005) describes the role of FtsZ in prokaryotic division.

Summary of "The Cell Cycle" by Associate Professor Zanda Daneberga

1. The Cell Cycle Overview

• The cell cycle is the cell's life cycle between divisions.
• It includes cell growth, DNA replication, and division, ensuring accurate cell reproduction for growth and tissue maintenance.

2. The Cell Cycle in Prokaryotes

• In prokaryotes, the cell cycle is mainly binary fission, where a cell duplicates its DNA and divides into two identical cells.
• Three phases:
  • Replication Phase (R-phase or C-period):
    • Bacterial genome is replicated (e.g., Escherichia coli takes 40 minutes).
  • Division Phase (D-phase or D-period):
    • Daughter chromosomes separate.
    • FtsZ proteins form a Z-ring at the cell midpoint, leading to septum formation.
  • Interval Phase (I-phase or B-period):
    • Time between cell division and the next replication cycle.
• FtsZ proteins control bacterial cytokinesis, regulating the division septum.

3. The Cell Cycle in Eukaryotes

• Eukaryotic cells have a complex cycle with DNA replication and cell division.
• Divided into interphase and mitosis (M phase).
  • Interphase:
    • Includes G1, S, and G2 phases.
    • G1 Phase (Gap 1):
    • Cell grows and produces RNA and proteins.
    • Prepares for DNA replication with checkpoints.
    • S Phase (Synthesis):
    • DNA is replicated, doubling the content.
    • Centrioles duplicate.
    • G2 Phase (Gap 2):
    • Cell checks for DNA damage and prepares for mitosis.
  • M Phase (Mitosis):
    • Cell physically divides into two identical cells.
  • GO Phase (Resting Phase):
    • Cells exit the cycle into a resting state.
    • Neuronal cells and red blood cells stay permanently in GO.
    • Some cells can re-enter the cycle (e.g., liver cells and lymphocytes).
    • GO cells can be:
    • Quiescent: Dormant but can reactivate.
    • Senescent: Aged cells that can't divide.
    • This phase balances cell proliferation and differentiation.

4. Specialized Cell Behaviors and Division Capabilities

• Cell division varies among different cell types:
  • Non-dividing Cells:
    • Mature red blood cells (RBCs) and neurons don't divide.
  • Inducible Cell Division:
    • Liver cells and lymphocytes can divide under certain conditions.
  • Cells with High Mitotic Activity:
    • Stem cells and epithelial cells divide constantly.

5. Timeframe of the Eukaryotic Cell Cycle

• Human cells take about 24 hours for a full cycle:
  • G1 phase: ~11 hours
  • S phase: ~8 hours
  • G2 phase: ~4 hours
  • M phase: ~1 hour
• Timing varies by cell type and conditions.

Key Insights:

• Prokaryotic cell cycle: binary fission with clear phases regulated by FtsZ protein.
• Eukaryotic cell cycle: multi-phase with checkpoints ensuring DNA integrity before mitosis.
• GO phase: maintains homeostasis by allowing cells to exit cycling when division isn't needed.
• Diversity in cell division: reflects functional specializations in tissues and organisms.

Core Concepts:

• Cell Cycle Phases: G1, S, G2, M, and GO explain how cells grow, replicate DNA, and divide.
• Binary Fission: simple division in prokaryotes using chromosome replication and Z-ring mediated septum formation.
• Cell Cycle Regulation: Checkpoints in G1 and G2 prevent genome instability.
• Cell Differentiation and Cycle Exit: GO phase conserves cell function in multicellular organisms.
• Protein Machinery: FtsZ in bacteria and centriole duplication in eukaryotes are essential for division.

Keywords:

• Cell cycle, binary fission, prokaryotes, eukaryotes, replication phase, division phase, interval phase, FtsZ protein, Z-ring, interphase, G1 phase, S phase, G2 phase, M phase, GO phase, quiescence, senescence, DNA synthesis, mitosis, cell division, differentiated cells, stem cells.

FAQ:

• Q1: What is the significance of the FtsZ protein in prokaryotic cell division?
  • A1: FtsZ forms a ring to initiate division by guiding septum formation.
• Q2: Why do some cells enter the GO phase?
  • A2: Cells enter GO when division is unnecessary, allowing them to perform specialized functions.
• Q3: How do eukaryotic cells ensure DNA is accurately replicated before division?
  • A3: Through checkpoints in G1 and G2 phases, cells verify DNA integrity and completeness.
• Q4: Can cells in GO re-enter the cell cycle?
  • A4: Yes, quiescent cells can re-enter if activated, but senescent cells cannot.
• Q5: How does the duration of cell cycle phases vary?
  • A5: Duration varies by cell type, but in human cells, the cycle is around 24 hours with specific phase durations as outlined above.

Chapter Summary

Core Points

• Definition and Overview of the Cell Cycle
  • The cell cycle is the life cycle of a cell between divisions.
  • Includes cell growth, DNA replication, and division, preserving cell and genetic integrity.
• Cell Cycle in Prokaryotes (Bacterial Cells)
  • Prokaryotes reproduce via binary fission with three phases:
  • a. Replication phase (R-phase or C-period): DNA replication (e.g., Escherichia coli takes 40 minutes).
  • b. Division phase (D-phase or D-period): Daughter chromosomes separate. FtsZ protein forms Z-ring.
  • c. Interval phase (I-phase or B-period): Time between cell division and new DNA replication.
• Molecular Mechanisms Driving Prokaryotic Cell Division
  • FtsZ protein forms a contractile Z-ring, initiating septum formation.
  • Chromosome replication and cell division are coordinated.
• Cell Division Capacity and Specialization in Eukaryotes
  • Eukaryotic cells vary in division capacity:
  • a. Non-dividing cells: red blood cells and neurons.
  • b. Inducible cells: liver cells and lymphocytes.
  • c. High mitotic activity: stem cells and epithelial cells.
• Phases of the Eukaryotic Cell Cycle
  • Divided into interphase and mitotic phase (M):
  • a. Interphase: G1, S, and G2 phases.
  • b. G1 phase: Cell growth and preparing for replication. Checkpoints occur.
  • c. S phase: DNA replication and centriole duplication.
  • d. G2 phase: Preparing for division and checkpoints to ensure error-free DNA replication.
  • e. M phase: Cell division.
• Resting and Exit States (GO Phase)
  • GO phase is a resting state:
  • a. Quiescent: Dormant but can re-enter the cycle.
  • b. Senescent: Permanently exiting the cycle.
  • Most somatic cells are in the GO phase.

Key Conclusions

• Binary Fission as an Efficient Prokaryotic Reproductive Strategy
  • Binary fission: streamlined for bacterial propagation regulated for survival.
• FtsZ and the Role of Cytoskeletal-Like Structures in Bacterial Division
  • FtsZ parallels eukaryotic systems.
• Eukaryotic Cell Cycle Complexity Supports Organismal Development and Tissue Maintenance
  • Multi-phased: fine control over cell proliferation.
• Cellular Differentiation Dictates Division Potential and Tissue Regeneration Capacity
  • Terminal differentiation: cells exit the cycle.
• GO Phase as a Critical Regulatory Node
  • GO state: balances cell proliferation with cell function.
• Checkpoint Mechanisms Ensure Genomic Stability
  • Checkpoints in G1 and G2 prevent damaged material propagation.

Important Details

• Timeframes for Eukaryotic Cell Cycle Phases
  • Human cell (24-hour cycle): G1 (~11 hours), S (~8 hours), G2 (~4 hours), and M (~1 hour).
• Checkpoint Function Variability
  • G1 variability: reflects responsiveness to environmental cues.
• Specialization and Division Control Correlations
  • Non-dividing cells stay in GO.
• DNA and Organelle Replication Coordination
  • S phase: DNA and centrioles duplicated.
• Senescence vs. Quiescence Distinctions
  • Only quiescent cells can re-enter proliferation.
• References Supporting Content
  • Wang and Levin (2009): metabolism and bacterial cell growth.
  • Margolin (2005): function of the FtsZ protein in cell division.
• Variability in Cell Cycle Among Species and Cell Types
  • Duration varies significantly.
• Importance of Mitosis (M Phase)
  • Nuclear and cytoplasmic division.
• Function of the Z-Ring in Cytokinesis
  • Z-ring recruits proteins.
• Cell Cycle as a Target for Medical Intervention
  • Target proliferative processes.
• Cell Cycle Exit Mechanisms Facilitate Differentiation and Homeostasis
  • GO phase maintains differentiated cell functions.
• Terminology Cross-Reference Between Prokaryotic and Eukaryotic Cell Cycles
  • Prokaryotic (B, C, D) vs. eukaryotic (G1, S, G2).

1. The Cell Cycle - DNA Reparation

• Organisms face DNA-damaging agents from internal and external sources.
• DNA damage threatens genomic integrity.
• DNA Repair systems correct lesions.
• Checkpoints monitor DNA integrity.
• Failures in checkpoints increase disease risk.

2. DNA Damage Response

• The DNA damage response (DDR) detects and signals DNA lesions.
• Activates checkpoint controls.
• Recruits DNA repair machinery.

3. DNA Damage Repair Mechanisms

• Include:
  • Mismatch Repair (MMR)
  • Nucleotide Excision Repair (NER)
  • Base Excision Repair (BER)
  • Double-strand break repair via Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ)

4. Mismatch Repair (MMR)

• Corrects replication errors.
• Corrects base mismatches.
• Excises erroneous DNA and resynthesizes.

5. Mismatch Repair (MMR) and Disease Associations

• Mutations in MMR genes can predispose to hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome.

6. Nucleotide Excision Repair (NER)

• Removes bulky DNA lesions.
• Two sub-pathways:
  • Transcription-Coupled NER (TC-NER)
  • Global Genomic NER (GG-NER)

7. NER and Human Pathologies

• Mutations cause Xeroderma Pigmentosum (XP).
• XP leads to extreme photosensitivity.

8. Cockayne Syndrome (CS) and NER

• Linked to defective NER pathways.
• Patients exhibit growth failure, retardation, photosensitivity, hearing loss, and premature aging.

9. Case Report of Cockayne Syndrome

• Male CS patient exhibited neurological degeneration from childhood, including motor impairments.

10. Molecular Basis of Cockayne Syndrome

• CS proteins play roles in transcription-coupled repair.
• Deficiencies lead to oxidative damage and premature aging.

11. Base Excision Repair (BER)

• Repairs small DNA lesions.
• Two BER pathways:
  • Short-patch BER
  • Long-patch BER

12. BER - Mechanistic Details and Disease Implications

• No human diseases are conclusively linked to BER defects.

13. Homologous Recombination Repair (HR) and Non-Homologous End Joining (NHEJ)

• Repair DNA double-strand breaks (DSBs).
• HR uses a homologous DNA template.
• NHEJ ligates broken ends directly.

14. Repair of Double Strand Breaks (DSB)

• Prevents chromosomal instability.

15. Human Pathologies Associated with HR and NHEJ Defects

• Defects in HR underlie cancer predisposition syndromes.
• Mutations in HR-associated genes linked to hereditary breast and ovarian cancers.

Cell Cycle - Regulation

• The cell cycle is a regulated series of events.
• Involves Cyclin-dependent kinases (CDKs).

Regulation of the Cell Cycle in Eukaryotes - CDKs

• Multiple cyclins associate with each CDK.
• Three primary cyclin-CDK complexes:
  • G1 cyclin-CDK: involved in early events.
  • S-phase cyclin-CDK: regulates DNA synthesis.
  • Mitotic cyclin-CDK: triggers events for mitosis.

CDKs

• G1-cyclin-CDK (Cyclin D-CDK4/6): Responds to growth factors and regulates PRB.
• Cyclin E-CDK2: Facilitates transition from G1 to S phase.
• S-phase cyclin-CDK (Cyclin A-CDK2/ CDK1): Prom