Dalvoy Logo
Dalvoy
UPSC MainsBOTANY-PAPER-II20245 Marks
Q7.

Molecular basis of cell cycle.

How to Approach

This question requires a detailed understanding of the molecular mechanisms governing the cell cycle. The answer should focus on key regulatory molecules like cyclins, cyclin-dependent kinases (CDKs), and their inhibitors (CKIs). It should also cover the checkpoints within the cell cycle and the signaling pathways involved. A structured approach, dividing the cell cycle into phases and explaining the molecular events in each phase, is recommended. Mentioning experimental evidence that led to these discoveries will add value.

Model Answer

0 min read

Introduction

The cell cycle is a fundamental process in all living organisms, ensuring accurate duplication and segregation of genetic material. It’s a highly regulated series of events comprising interphase (G1, S, and G2 phases) and M phase (mitosis and cytokinesis). Disruptions in cell cycle control can lead to uncontrolled cell proliferation, a hallmark of cancer. Understanding the molecular basis of the cell cycle is crucial for comprehending development, tissue homeostasis, and disease pathogenesis. The discovery of cyclins and CDKs revolutionized our understanding of cell cycle regulation, earning Leland Hartwell, Paul Nurse, and Tim Hunt the Nobel Prize in Physiology or Medicine in 2001.

The Cell Cycle and its Phases

The cell cycle is broadly divided into four phases: G1 (gap 1), S (synthesis), G2 (gap 2), and M (mitosis). Each phase is characterized by specific molecular events. The progression through these phases is tightly regulated by checkpoints, ensuring the fidelity of DNA replication and chromosome segregation.

Key Molecular Players

Cyclins

Cyclins are a family of proteins whose concentration fluctuates cyclically during the cell cycle. Different cyclins are expressed at different phases and bind to and activate CDKs.

Cyclin-Dependent Kinases (CDKs)

CDKs are serine/threonine kinases that are inactive unless bound to a cyclin. Once activated, CDKs phosphorylate target proteins, driving the cell cycle forward. Different cyclin-CDK complexes regulate different phases of the cell cycle.

CDK Inhibitors (CKIs)

CKIs are proteins that bind to cyclin-CDK complexes, inhibiting their activity. They play a crucial role in regulating cell cycle progression and responding to cellular stress.

Molecular Events in Each Phase

G1 Phase

The G1 phase is a period of growth and preparation for DNA replication. The key regulator here is the G1 cyclin-CDK complex (Cyclin D-CDK4/6). This complex phosphorylates the Retinoblastoma protein (Rb), releasing the E2F transcription factor, which then activates genes required for S phase entry. CKIs like p21 and p27 can inhibit G1 cyclin-CDK complexes, arresting the cell cycle.

S Phase

The S phase is characterized by DNA replication. Cyclin E-CDK2 initiates DNA replication, and Cyclin A-CDK2 helps complete it. The origin recognition complex (ORC) binds to origins of replication, initiating the process. DNA polymerase and other replication proteins are essential for accurate DNA synthesis.

G2 Phase

The G2 phase is a period of growth and preparation for mitosis. Cyclin B-CDK1 (also known as MPF - Maturation Promoting Factor) is the key regulator. It phosphorylates proteins involved in chromosome condensation, nuclear envelope breakdown, and spindle formation. The G2/M checkpoint ensures that DNA replication is complete and DNA damage is repaired before entering mitosis.

M Phase

The M phase consists of mitosis and cytokinesis. Cyclin B-CDK1 drives the cell through mitosis. The Anaphase Promoting Complex/Cyclosome (APC/C) is a ubiquitin ligase that targets securin for degradation, allowing separase to cleave cohesin and initiate sister chromatid separation. Cytokinesis, the division of the cytoplasm, is driven by the formation of a contractile ring composed of actin and myosin.

Checkpoints in the Cell Cycle

Checkpoints are control mechanisms that ensure the fidelity of cell cycle progression. The major checkpoints include:

  • G1 Checkpoint: Monitors cell size, nutrient availability, and DNA damage.
  • G2/M Checkpoint: Ensures DNA replication is complete and DNA damage is repaired.
  • Spindle Assembly Checkpoint (SAC): Ensures all chromosomes are properly attached to the spindle before anaphase.

Signaling Pathways Involved

Several signaling pathways regulate the cell cycle, including:

  • MAPK pathway: Involved in G1 phase progression.
  • PI3K/Akt/mTOR pathway: Promotes cell growth and survival.
  • p53 pathway: Activated in response to DNA damage, leading to cell cycle arrest or apoptosis.
Phase Key Cyclin-CDK Complex Major Events
G1 Cyclin D-CDK4/6 Rb phosphorylation, E2F activation, gene expression
S Cyclin E-CDK2, Cyclin A-CDK2 DNA replication
G2 Cyclin B-CDK1 Chromosome condensation, nuclear envelope breakdown
M Cyclin B-CDK1 Mitosis, cytokinesis

Conclusion

The molecular basis of the cell cycle is a complex and tightly regulated process. Cyclins, CDKs, and CKIs are central to this regulation, orchestrating the events of each phase and ensuring the accurate duplication and segregation of genetic material. Understanding these mechanisms is crucial for comprehending normal development and disease, particularly cancer. Further research continues to unravel the intricacies of cell cycle control, offering potential targets for therapeutic intervention.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Evaluate your handwritten answer in under a minute

Free trial available • Trusted by 1,00,000+ aspirants

Additional Resources

Key Definitions

Cyclin-Dependent Kinases (CDKs)
Serine/threonine kinases that require binding to a cyclin for activation and play a crucial role in regulating cell cycle progression.
Checkpoints
Control mechanisms within the cell cycle that ensure the fidelity of DNA replication and chromosome segregation, halting progression if errors are detected.

Key Statistics

Approximately 30% of human cancers are associated with defects in cell cycle control genes (Source: National Cancer Institute, knowledge cutoff 2023).

Source: National Cancer Institute

Approximately 85-90% of human cells are in the G1 phase of the cell cycle (Source: Alberts et al., Molecular Biology of the Cell, 6th edition, 2015).

Source: Alberts et al., Molecular Biology of the Cell

Examples

Retinoblastoma (Rb) and Cell Cycle Control

Loss of function mutations in the Rb gene are frequently observed in retinoblastoma, a childhood eye cancer. Rb normally inhibits the cell cycle by binding to E2F. When Rb is mutated, E2F is constitutively active, leading to uncontrolled cell proliferation.

Frequently Asked Questions

▶What is the role of p53 in cell cycle control?

p53 is a tumor suppressor protein activated in response to DNA damage. It can induce cell cycle arrest (allowing time for DNA repair) or apoptosis (programmed cell death) if the damage is irreparable, preventing the propagation of mutated cells.

Back to all BOTANY-PAPER-II 2024 questions