Genetic Material: Key Characteristics

• Contains complex information
• Replicates faithfully
• Encodes phenotype
• Has the capacity to vary

Evidence DNA is the Genetic Material

• Griffith transformation: Type IIIS (virulent) vs Type IIR (nonvirulent) bacteria in mice
• Heat-killed IIIS + IIR mix transforms IIR into IIIS-like phenotype
• Enzymatic treatments show the transforming substance is DNA (DNase blocks transformation; protease/RNase do not)
• Conclusion: DNA is the genetic material

DNA Structure: Core Concepts

• Structure: double helix (two antiparallel strands)
• Backbone: sugar (deoxyribose) + phosphate
• Bases pair via hydrogen bonds: A–T and G–C
• A–T pairs: 2 hydrogen bonds; G–C pairs: 3 hydrogen bonds
• Strands run in opposite directions (antiparallel)
• In RNA, uracil replaces thymine; sugar is ribose

Nucleotides and Bases

• Nucleotide composition: sugar (deoxyribose), phosphate, nitrogenous base
• Four bases in DNA: A, C, G, T
• Purines: A and G; Pyrimidines: C and T
• Base-pairing rules: A pairs with T, G pairs with C

DNA Backbone and Orientation

• Phosphodiester linkage connects 5'-phosphate to 3'-OH
• 5' end vs 3' end define strand orientation
• Bases reside on the interior of the ladder; sugar-phosphate backbone on the exterior

DNA Replication: Semiconservative Copying

• Replication must be highly accurate: about one error per 10^6 nucleotides
• E. coli replication rate: ~1000 nucleotides per second
• Requirements: template strand, raw materials (nucleotides), enzymes/proteins
• Semiconservative model: each daughter DNA has one old and one new strand

Nucleotide Precursors and Synthesis

• New DNA synthesized from deoxyribonucleoside triphosphates (dNTPs)
• dNTPs feature three phosphates; energy for bond formation comes from releasing two phosphates

Directionality of Synthesis

• DNA polymerase adds nucleotides to the 3' end of the growing strand
• Synthesis proceeds 5' → 3' on the new strand
• Template reads 3' → 5' during synthesis

Leading and Lagging Strands

• Leading strand: continuous synthesis toward the replication fork
• Lagging strand: discontinuous synthesis away from fork via Okazaki fragments
• Primase synthesizes RNA primers to provide 3'-OH for DNA polymerase
• DNA polymerase I replaces RNA primers with DNA nucleotides; DNA ligase seals the remaining nick

Telomeres and End-Replication Problem

• Linear chromosomes create a end-replication problem; primers leave gaps at ends
• Telomeres: repetitive ends that protect chromosome ends
• Telomerase: ribonucleoprotein that extends telomeres using its RNA template
• Most somatic cells have low telomerase activity; reactivation can lead to immortalization
• Telomerase activity is common in cancer cells (≈90% of cancers)

Telomeres, Disease, and Aging

• Werner syndrome illustrates telomere maintenance defects and aging-related issues

Central Dogma: Information Flow

• DNA information transferred to RNA, then to protein (via genetic code)
• In some viruses, information can flow from RNA to DNA or to another RNA
• Up next: Transcription and Translation

Quick Review Questions (with answers)

• Question 1: If protein carried hereditary information, which enzyme would stop transformation? Answer: A. DNAse
• Question 2: Which are purines? Answer: D. adenine and guanine
• Question 3: Which base pair would be stronger? Answer: G–C
• Question 4: What does 5' and 3' refer to? Answer: The number of carbon atoms of deoxyribose involved in phosphodiester bonds
• Question 5: How many phosphates are attached to a nucleotide that can be added to a growing strand? Answer: D. 3
• Question 6: Direction of template strand reading during synthesis? Answer: 3' to 5'
• Question 7: Which strand is synthesized in the opposite direction from unwinding? Answer: lagging strand
• Question 8: If a DNA is 10% A, what is % T? Answer: 10%
• Question 9: If a DNA is 10% A, what is % C? Answer: 40%