molecular inheritance

• Darwin publishes "The Origin of Species"


  1859
• Mendel publishes "Experiments in Plant Hybridization"


  1866
• Early 1900's: Mendel's experiments are replicated
• The idea of the chromosome is put forth
• T.H. Morgan develops idea that genes are located on chromosomes (made of DNA and protein)


  1904 - 1927
• Frederick Griffith develops transformation (transferring a genetic trait from one organism to another)


  1928
• Avery, McCarty, MacLeod announce that chromosomes are made of nucleotides (the transforming substance is DNA)


  1944
• Alfred Hershey & Martha Chase show that DNA is the genetic material


  1952
• Bacteriophages


  Viruses that infect bacteria
• The T2 phage is made of a protein coat and DNA
• 35S only labels protein, 32P only labels DNA
• The genetic material is inserted into the bacteria cell by the phage
• Hershey & Chase show that DNA is the genetic material
• Erwin Chargaff found in any organism the amount of A = T, and the amount of G = C, eventually leading to Chargaff's rules


  1947
• Linus Pauling, Rosalind Franklin, Maurice Wilkins, James Watson, and Francis Crick were involved in the discovery of the structure of DNA
• James Watson and Francis Crick published their findings in Nature in 1953
• Watson, Crick, and Wilkins were awarded the Nobel Prize in 1962
• Nucleotide monomers


  Pyrimidines (T, C) and purines (A, G)
• Sugar-phosphate backbone


  Nucleotides linked by phosphodiester bonds
• 5' and 3' ends


  Directionality of the DNA strand
• The DNA strands are antiparallel
• Hydrogen bonding


  Bonds between complementary base pairs (A-T, G-C)
• Watson and Crick initially thought the bases would pair like with like, but this did not result in a uniform width
• The DNA structure is a right-handed antiparallel double helix held together by hydrogen bonded complementary base pairing
• 3 Main Models of DNA Synthesis

  • Conservative
  • Semiconservative
  • Dispersive
• The semiconservative model was proposed by Crick and Watson in 1954
• Meselson and Stahl demonstrated the semiconservative model


  1958
• Origins of replication


  Specific sites where the two DNA strands separate to initiate replication
• DNA Replication


  1. Initiation: Replication begins at origins, forming replication bubbles

  2. Elongation: DNA polymerase adds nucleotides to the leading and lagging strands

  3. Termination: Replication bubbles fuse, completing synthesis of daughter strands
• Replication fork


  Region where the two parental strands separate and new daughter strands are synthesized
• Topoisomerase, Primase, Helicase, Single-strand binding proteins


  Enzymes and proteins involved in DNA replication
• Leading strand


  DNA strand synthesized continuously in the 5' to 3' direction
• Lagging strand


  DNA strand synthesized discontinuously in the 5' to 3' direction, forming Okazaki fragments
• DNA polymerase


  Enzyme that catalyzes the dehydration synthesis of new DNA by adding nucleotides to a preexisting chain
• dNTPs


  Deoxyribose nucleoside triphosphates, the substrates for DNA synthesis
• DNA polymerase III adds nucleotides to the leading strand starting from the original RNA primer
• Lagging strand synthesis


  Primase makes RNA primer, DNA polymerase III synthesizes Okazaki fragments, DNA polymerase I replaces RNA with DNA, DNA ligase seals the gaps
• DNA Synthesis: Elongation


  1. Leading Strand: DNA Polymerase III adds nucleotides starting off of the original RNA primer

  2. Lagging Strand: Primase makes RNA primer, DNA Pol III makes Okazaki fragments
• Primase


  Makes RNA primer
• DNA Synthesis: Elongation


  1. Leading Strand: DNA Pol III makes continuous synthesis in 5' to 3' direction

  2. Lagging Strand: Primase makes RNA primer, DNA Pol III makes Okazaki fragments, DNA Pol I replaces RNA with DNA, DNA ligase forms bonds between DNA fragments