Biology Topic 3

• Watson and Crick Model of DNA


  The 3-dimensional structure of DNA discovered in 1953

  
• Learning objectives (LOBs)


  • Describe the structure and functions of DNA
  • Describe the structure of chromosomes, including the structure and organisation of chromatin
  • Describe the process of DNA replication, including the processes of telomere replication and DNA repair
• The identification of the molecules of inheritance was a major challenge to biologists in the 20th century
• Morgan's group showed that genes are located on chromosomes
• Protein was a stronger candidate than DNA for the genetic material
• Characteristics the genetic material needed to have

  • Contain information
  • Be easy to copy
  • Be variable to account for diversity between species
• The role of DNA in heredity was first discovered by studying bacteria and viruses
• Griffith's experiment provided evidence that DNA can transform bacteria
• Hershey and Chase's experiments provided evidence that viral DNA can program cells
• Erwin Chargaff reported that DNA composition varies between species
• Maurice Wilkins and Rosalind Franklin used X-ray crystallography to study the molecular structure of DNA

  
• Watson and Crick produced the double-helical model for DNA structure based on Franklin's X-ray crystallographic images

  
• DNA structure


  • 2 antiparallel sugar-phosphate backbones
  • Nitrogenous bases pairs are in the molecule's interior

  
• Watson and Crick determined that adenine (A) paired only with thymine (T), and guanine (G) paired only with cytosine (C)

  
• Chargaff's rule: in any species there is an equal number of A and T bases and an equal number of G and C bases
• DNA is the substance of inheritance
• Hereditary information is encoded in DNA and reproduced in all the cells of the body
• DNA has 2 polynucleotides spiraling around an imaginary axis, forming a double helix

  
• DNA nucleotide


  Consists of a nitrogenous base, a pentose sugar (deoxyribose), and a phosphate group

  
• Nucleoside


  Nitrogenous base + pentose sugar
• In DNA, the sugar is deoxyribose
• Phosphodiester bond


  Bond between the 3'-OH group of the sugar molecule of one nucleotide and the 5'-phosphate group of the second nucleotide

  
• Bacterial chromosomes are circular double-stranded DNA molecules associated with a small amount of protein

  
• Eukaryotic chromosomes are double stranded linear DNA molecules associated with a large amount of proteins (histones)

  
• Chromatin


  DNA + histones (proteins)

  
• Levels of chromatin packing in a eukaryotic chromosome

  • DNA wrapped around nucleosomes as "beads on a string" (10-nm fiber)
  • Looped domains (300-nm fiber)
  • Metaphase chromosome (1,400 nm)

  
• Nucleosome


  Consists of 8 histone molecules (H2A, H2B, H3, H4)2 + ds DNA (168 base pairs)

  
• H1 histone


  Located between the nucleosomes, role is to stabilize the interaction between DNA and nucleosomal histones

  
• Euchromatin


  Loosely packed chromatin (active form), enables replication and transcription, enables gene expression
• Heterochromatin


  Highly condensed chromatin (inactive form), inhibits replication and transcription, inhibits gene expression
• Chromatin changes in packing during the cell cycle

  1. During interphase: Most chromatin is loosely packed (euchromatin)

  2. During mitosis: chromatin is highly condensed into heterochromatin
• Histone modification


  Chemical modifications (e.g. methylation, acetylation) that result in changes in chromatin organization and gene expression
• Epigenetics


  The study of cellular/physiological traits that are NOT caused by changes in the DNA sequence, but by changes in gene expression (e.g. DNA methylation, histone modification)
• 30-nm fiber


  Chromatin structure during mitosis
• Chromatin structure and organisation during mitosis

  1. Chromatin is highly condensed into heterochromatin

  2. Inhibition of gene expression

  3. Exception: centromeres and telomeres are always highly condensed into heterochromatin
• Histone modification can result in gene silencing (inhibition of gene expression)
• Histone modification is involved in many diseases (e.g. cancer)
• Epigenetics


  The study of cellular/physiological traits that are NOT caused by changes in the DNA sequence, but caused by changes in gene expression
• Epigenetic mechanisms


  • DNA methylation
  • Histone modification
• Histone acetylation


  • Converts heterochromatin into euchromatin
  • Loss of the histone (+) charge due to acetylation weakens their interaction with DNA
  • Converts chromatin into its loose active form (euchromatin)
  • Enables gene expression