Makindo Medical Notes

Related Subjects: |DNA and RNA short notes |DNA replication |DNA structure in Nucleus |Mitosis and Meiosis |Telomeres |Autosomal Recessive |X Linked Recessive |Autosomal Dominant |Li Fraumeni syndrome |Genetic Linkage |Cell Cycle

Chargaff's rules: In double-stranded DNA ➡️ %A = %T and %G = %C. Purines = Pyrimidines overall. These base-pairing rules were known before Watson & Crick’s helix model.

🧱 Building Blocks

• Purines (2 rings): Adenine (A), Guanine (G). Synthesis requires glycine, aspartate, glutamine.
• Pyrimidines (1 ring): Cytosine (C), Thymine (T in DNA), Uracil (U in RNA).
• Base pairing → Purine + Pyrimidine (3 rings across) maintains uniform helix width.

📜 Nucleic Acids

• DNA: A=T (2 H-bonds), G≡C (3 H-bonds — stronger!).
• RNA: A=U, G≡C. Usually single-stranded.
• Sugars: DNA = deoxyribose; RNA = ribose (extra OH → less stable).
• Human diploid genome = 23 chromosome pairs.
• DNA → nuclear; RNA → 90% cytoplasmic.

🔬 Types of RNA

• mRNA: Protein template. 5′ cap + 3′ poly(A) tail = stability & translation.
• tRNA: Cloverleaf adaptor carrying amino acids (anticodon matches codon).
• rRNA: Structural + catalytic core of ribosomes (peptidyl transferase activity).

📆 Eukaryotic Cell Cycle

• G0: Resting phase (neurons, RBCs stay here permanently).
• G1: Growth, organelle duplication. Restriction point checks DNA damage.
• S: DNA replication. Centrosome duplication.
• G2: Error checking before mitosis.
• M: Mitosis (prophase → telophase + cytokinesis).

⚡ DNA Replication

• Semiconservative: 1 parental + 1 new strand.
• DNA polymerase: works 5′→3′; needs an RNA primer.
• Leading strand: continuous synthesis.
• Lagging strand: Okazaki fragments (later ligated).
• Error rate: ~1 per 10¹⁰ bases (proofreading via 3′→5′ exonuclease).
• mtDNA: circular, maternal inheritance.
• Proto-oncogenes regulate cycle; mutations → oncogenes → cancer.

🔄 Quality Control

• Checkpoints (cyclins + CDKs regulate):
  • G1/S: “restriction point” – damaged DNA? nutrients sufficient?
  • G2/M: DNA replicated? errors fixed?
  • Metaphase checkpoint: spindle attachment?

⏳ Telomeres

• Repeat sequences (TTAGGG in humans) protect chromosome ends.
• Shorten with each division → cellular aging (“replicative senescence”).
• Germline, stem, and cancer cells express telomerase → immortality.

⚡ Energy for Replication

• Energy comes from hydrolysis of nucleoside triphosphates → pyrophosphate release drives chain elongation.
• Strand growth always at the 3′ end.
• Diagram: Okazaki fragments

📌 Quick Exam Summary

🧬 A=T (2 bonds), G≡C (3 bonds). 📆 Cell cycle checkpoints stop faulty replication. ⚡ Replication is semiconservative, 5′→3′, with leading vs lagging strands. ⏳ Telomeres shorten with age unless telomerase is active. 💥 Oncogenes = mutated proto-oncogenes → unchecked growth.