M03.06.03 CLONING GENES AS cDNA PRODUCED BY REVERSE TRANSCRIPTION OF CELLULAR mRNA

The cell cycle and apoptosis are fundamental biological processes governing cell proliferation and death. Understanding these processes is crucial for medical students, as dysregulation can lead to diseases such as cancer. This detailed exploration includes tables, side notes with key points, and a bibliography for further reading.

Cell Cycle

The cell cycle is the series of events that cells go through as they grow and divide. It consists of distinct phases:

1. G1 Phase (Gap 1)
   • Description: The cell grows and synthesizes proteins necessary for DNA replication.
   • Key Events: Cell growth, organelle duplication.
   • Duration: Variable, can be hours to years.
2. S Phase (Synthesis)
   • Description: DNA replication occurs, resulting in two identical sister chromatids for each chromosome.
   • Key Events: DNA synthesis, replication of centrosomes.
   • Duration: Approximately 6-8 hours.
3. G2 Phase (Gap 2)
   • Description: The cell continues to grow and prepares for mitosis.
   • Key Events: Synthesis of proteins required for mitosis, correction of DNA replication errors.
   • Duration: 4-6 hours.
4. M Phase (Mitosis)
   • Description: Division of the nucleus and the cytoplasm to form two daughter cells.
   • Key Events:
     • Prophase: Chromosomes condense, and spindle fibers form.
     • Metaphase: Chromosomes align at the metaphase plate.
     • Anaphase: Sister chromatids separate to opposite poles.
     • Telophase: Nuclear envelopes re-form, chromosomes decondense.
   • Duration: 1-2 hours.
5. Cytokinesis
   • Description: Division of the cytoplasm, resulting in two distinct daughter cells.
   • Key Events: Cleavage furrow forms (in animal cells), cell plate forms (in plant cells).

Cell Cycle Regulation

The cell cycle is tightly regulated by various checkpoints to ensure proper division:

1. G1 Checkpoint
   • Purpose: Determines if the cell has enough resources and proper signals to enter the S phase.
   • Key Regulators: Cyclins, Cyclin-dependent kinases (Cdks), Retinoblastoma protein (Rb).
2. G2 Checkpoint
   • Purpose: Ensures all DNA is replicated and undamaged before mitosis.
   • Key Regulators: p53, Cyclins, Cdks.
3. M Checkpoint (Spindle Checkpoint)
   • Purpose: Ensures all chromosomes are properly attached to the spindle fibers before anaphase.
   • Key Regulators: Anaphase-promoting complex/cyclosome (APC/C).

Apoptosis

Apoptosis, or programmed cell death, is a critical process for maintaining cellular homeostasis and eliminating damaged cells. It involves a cascade of biochemical events leading to characteristic cell changes and death.

1. Intrinsic Pathway (Mitochondrial Pathway)
   • Trigger: Internal signals such as DNA damage, and oxidative stress.
   • Key Events: Release of cytochrome c from mitochondria, activation of caspases.
   • Regulators: Bcl-2 family proteins (pro-apoptotic and anti-apoptotic).
2. Extrinsic Pathway (Death Receptor Pathway)
   • Trigger: External signals such as Fas ligand binding to death receptors.
   • Key Events: Activation of death receptors, formation of death-inducing signaling complex (DISC), activation of caspases.
   • Regulators: Death receptors (Fas, TNF receptor).

Key Points to Memorize

• Cell Cycle Phases: Understand the sequence and key events of G1, S, G2, M phases, and cytokinesis.
• Checkpoints: Remember the purpose and key regulators of G1, G2, and M checkpoints.
• Apoptosis Pathways: Distinguish between intrinsic and extrinsic pathways, their triggers, and key events.

Bibliography

1. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular Biology of the Cell (4th ed.). Garland Science.
2. Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). Biochemistry (5th ed.). W. H. Freeman.
3. Lodish, H., Berk, A., Kaiser, C. A., Krieger, M., Scott, M. P., Bretscher, A., & Ploegh, H. (2007). Molecular Cell Biology (6th ed.). W. H. Freeman.
4. Watson, J. D., Baker, T. A., Bell, S. P., Gann, A., Levine, M., & Losick, R. (2013). Molecular Biology of the Gene (7th ed.). Cold Spring Harbor Laboratory Press.
5. Voet, D., Voet, J. G., & Pratt, C. W. (2016). Principles of Biochemistry (5th ed.). Wiley.