Chapter 11: DNA Replication and Cell Division

1. Overview of Cell Division

• Definition: The process by which cells produce new cells.

• Functions:

  • Cell growth.

  • Cell replacement.

  • Cell healing.

  • Asexual reproduction.

2. Binary Fission in Bacteria

• Step-by-step process of binary fission:

  1. DNA attachment: Circular DNA molecule attaches to the inner membrane.

  2. DNA replication: Starts at a specific site, proceeds bidirectionally.

  3. Elongation: Newly synthesized DNA is attached to the membrane.

  4. Cell elongation: DNA attachment sites separate as the cell elongates.

  5. Constriction: Forms at the cell midpoint, leading to daughter cell formation.

  6. Completion: Cell membrane and wall synthesis separates two daughter cells.

3. Comparison of Eukaryotic and Prokaryotic Cell Division

• Eukaryotes: Large linear genome, DNA in the nucleus.

• Prokaryotes: Small circular genome, DNA in the cytoplasm.

• Similarities: DNA replication processes are analogous.

• Differences: Presence of nucleus and genome size affect division processes.

4. The Eukaryotic Cell Cycle

• Phases:

  1. M phase: The parent cell divides into two.

  2. Interphase: Between M phases, consists of:

     • G1 phase: cell growth and regulatory protein expression.

     • S phase: DNA synthesis.

     • G2 phase: preparation for mitosis.

     • G0 phase: resting phase with no division preparation.

5. DNA Replication Hypotheses

• Semiconservative model: Each new DNA duplex contains one original strand and one new strand.

• Conservative model: New DNA consists of two newly synthesized strands.

6. Research on DNA Replication

• Meselson and Stahl experiment: Utilized isotopes of nitrogen to validate the semiconservative model.

• After replication, if semiconservative, all DNA should show a mix of densities: one strand containing 15N and the other 14N.

7. Mechanisms of DNA Replication

• Proteins involved:

  • DNA polymerase: extends RNA primers.

  • Helicase: unwinds DNA strands.

  • Topoisomerase II: alleviates strain during unwinding.

  • Single-strand binding protein: stabilizes unwound DNA.

• Directionality: DNA strands replicated from 5′ to 3′, with mechanisms for proofreading.

• Leading vs. Lagging Strand:

  • Leading strand is synthesized continuously.

  • Lagging strand synthesized discontinuously in Okazaki fragments.

8. Lagging Strand Synthesis

• Okazaki fragments: Short pieces on the lagging strand formed due to the need for RNA primers and the 5′ – 3′ synthesis direction.

• RNA primers: Necessary for initiation of DNA synthesis.

• DNA ligase: Joins Okazaki fragments by completing the sugar-phosphate backbone.

9. Features of DNA Structure

• Antiparallel strands: Necessitates the leading and lagging strand synthesis.

10. Telomeres and Telomerase in Eukaryotes

• Telomeres: Ends of linear chromosomes containing repeated sequences.

• Telomerase: Enzyme that extends telomeres, mitigating loss during replication.

11. Checkpoints and Regulation of Cell Division

• CDK/Cyclin complexes: Regulate progression through the cell cycle.

• Cell Cycle Checkpoints:

  • DNA damage checkpoint.

  • DNA replication checkpoint.

  • Spindle assembly checkpoint.

• p53 protein: Involved in DNA damage response, can lead to apoptosis if damage is irreparable.

12. Cancer Biology

• Cancer: Uncontrolled cell division often due to mutations in proto-oncogenes or tumor suppressor genes.

  • Oncogenes: Mutated genes that promote excessive cell division.

  • Tumor suppressors: Proteins that normally inhibit cell division.

13. Summary of Cell Division Steps

1. Prophase: Chromosomes condense, mitotic spindle forms.

2. Prometaphase: Microtubules interact with chromosomes.

3. Metaphase: Chromosomes align at the cell equator.

4. Anaphase: Sister chromatids are pulled apart.

5. Telophase: Nuclear membrane re-forms, chromosomes decondense; cytokinesis occurs.

14. Importance of Cell Signaling

• Cells communicate using signaling molecules, which activate responses through cellular junctions and pathways.

• Cell adhesion: Vital for tissue integrity, involving various junction types.