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					• DNA and
  Chromosomes
      Genes are carried by
        Chromosomes
 Two plant cells visualized by
light microscope, DNA stained
          with DAPI

  Chromosome in Cells
DNA (deoxyribonucleic acid)
         AGTC
 Human 46 chromosomes
  22 homologs, x, or x/y
Experimental procedures demonstrating that DNA is the genetic material
                              1940s
     The Structure and Function of DNA
• Genetic information is carried in the linear sequence of
  nucleotides in DNA
• Genetic information contains instructions to synthesize
  proteins
• DNA forms double helix with two complimentary strands
  holding together by hydrogen bonds between A-T (2
  bonds) and G-C (3 bonds)
• DNA duplication occurs using one strand of parental DNA
  as template to form complimentary pairs with a new DNA
  strand.
• DNA is in nucleus in eucaryotes
     1953 Watson and Crick
determined the structure of DNA

    DNA and its Building
  Nucleotides: Guanine (G),
  Adenine (A), Cytosine (C),
        Thymine (T).
   Polarized strand, 5’->3’
  Base inside, sugar outside
DNA and its Building
 Antiparallel strands
     DNA Pairs
A always pairs with T,
    and G with C,
 A-T two hydrogen
  bonds, G-C three
   hydrogen bonds
               DNA Double Helix
10.4 nucleutides/turn; 3.4 nm between nucleutides
                        DNA to Protein
 Genome: the complete set of information in an organism’s DNA
Total length of DNA about 2 meters long in a human cell, encoding
                      about 30000 proteins
To carry the genomic information to daughter cells
                DNA Duplication
              Using itself as template
 Cell Nucleus, compartmentalized
          DNA activity
Nuclear pores allow communication
 Nuclear lamina and cytoskeleton
 mechanically support the nucleus
    Chromosomal DNA and its Packaging
• A gene is a nucleotide sequene in a DNA molecule that act as
  a functional unit for protein production, RNA synthesis.
• Introns and Exons
• Chromosome: single long DNA contains a linear array of
  many genes.
• Human genome contains 2.3x109 DNA nucleotide pairs, with
  22 different autosomes and 2 sex chromosomes.
• Chromosomal DNA: replication origins, telomeres,
  centromeres
• Histones form the protein core for DNA wrapping
• Nucleosome: repeating array of DNA-protein particles
• Modification of Chromatin and nucleosomes: histone H1,
  ATP-driven chromatin remodeling complexes, and
  enzymatically catalyzed covalent modification of the N-
  terminal tails of Histones
                    Human Chromosome
       Complex of DNA and protein is called chromatin
    44 homologous chromosomes and 2 sex chromosomes
          Complementary DNA with different Dyes
The arrangement of the full chromosome set is called karyotype
 Banding Pattern of
human chromosomes
  Giemsa Staining
 Green line regions:
    centromeres


           Encoding ribosome
The organization of genes of a human chromosome
   Conservation between human and mouse genomes
Usually important genes are encoded by conserved regions
 Note: Human chromosome 1 and mouse chromosome 4
          human                      mouse
                 centromere
                            Cell Cycle
DNA molecule not only carries genetic information, but also undergoes
                     conformational change
              Chromosomes exist through the cycle
               Mitotic and interphase chromosome
      Single chromosome can only be visible during mitosis
Chromosomes at
interphase and M
      phase
   Three important DNA sequences
Telomere, replication origin, centromere
        DNA Molecules are highly condensed in chromosomes
        Nucleosomes of interphase under electron microscope
    Nucleosome: basic level of chromosome/chromatin organization
                 Chromatin: protein-DNA complex
                    Histone: DNA binding protein
A: diameter 30 nm; B: further unfolding, beads on a string conformation
Nucleosome Structures
  Histone octamer
       2 H2A
       2 H2B
        2 H3
        2 H4
 X-ray diffraction analyses of crystals
Structure of a nucleosome core particle
Structural Organization of the Core Histones
The Assembly of the Core Histones
Notice the long tails of the octamer
               The bending of DNA in a nucleosome
1. Flexibility of DNAs: A-T riched minor groove inside and G-C
                      riched groove outside
                2. DNA bound protein can also help
Zigzag model of the 30-nm chromatin fiber
                  Irregularities in the 30-nm fiber
               Flexible linker, DNA binding proteins
Structural modulators: H1 histone, ATP-driven Chromatin remodeling
            machine, covalent modification of histone tails
The function of Histone H1
The function of
 Histone tails
Chromatin Remodeling
   Cyclic Diagram for
nucleosome formation and
       disruption
Covalent Modification
 of core histone tails
Acetylation of lysines
Mythylation of lysines
 Phosphorylation of
       serines

    Histone acetyl
  transferase (HAT)
 Histone deacetylase
       (HDAC)
                 Summary
•   DNA, Chromosome
•   Centromere, telomere, replication origin
•   Nucleosome, Chromatin,
•   Histone: H1, H2A, H2B, H3, H4
•   Histone octamer, DNA packaging
•   DNA binding proteins, Histone
    modifications
The Global Structure of Chromosomes
   • Some rare cases of interphase
     chromosomes, certain features maybe
     universal
   • Representative forms forming typical
     interphase chromosome
   • Chromosome at mitosis
Lampbrush chromosomes (amphibian oocyte, immature eggs)
  A model for the structure of a
     lampbrush chromosome
Chromomeres: highly condensed
and in general not expressed until
            unfolding
A polytene chromosome from
 Drosophila salivary gland
 Dark bands and interbands
Electron Microscope image of Drosophila polytene chromosome
      Chromosome puffs
Folding and refolding at a time
      course of 22 hours
        RNA synthesis in Chromosome puffs
Red: newly synthesized BrUTP; Blue: old ones diffused
RNA synthesis in Chromosome puffs
RNA synthesis in Chromosome puffs
Model of RNA synthesis in Chromosome puffs
A model for the structure of an
   interphase chromosome
 Position Effects on Gene
        Expression
Heterochromatin: condensed
    Euchromatin: loose
   Speculative Model for the heterochromatin at the ends of yeast
                            chromosomes
Sir: Silent information regulator binding to unacetylated histone tails
      Speculative Model for the heterochromatin at the ends of yeast
                              chromosomes
DNA-binding proteins recognize DNA sequence close to telomere, recruit
Sir proteins and cause histone tail modification, forming heterochromatin
 Two speculative models for how the tight packaging of DNA in
heterochromatin can be inherited during chromosome replication
The specialized nucleosome formed on centromeres
         Also belongs to heterochromatin
 The structure of a human
         centromere
  1. Alpha satellite DNA
           sequence
2. Kinetochore inner plate
3. Kinetochore outer plate
 4. Spindle microtubules
The plasticity of human centromere formation
A typical mitotic chromosome at
           metaphase
SEM of a region near one
 end of a typical mitotic
      chromosome
EM of a mitotic
 chromosome
     Chromatin Packing
Condensin plays important roles
The SMC (Structural Maintenance
  of Chromosomes) proteins in
          condensins
Selective localization of two interphase chromosomes
      Chromosome 18 (red) and 19 (turquoise)
Specific regions of interphase chromosomes in close proximity to the
                           nuclear envelope
Two different regions of chromosome 2 (yellow and magenta) close to
                      the nuclear envelop (green)
                   Summary
• Chromosomes are decondensed during interphase and
  hard to visualize
• Lampbrush chromosomes of vertebrate oocytes and
  polytene chromosomes in the giant secretory cells of
  insects are exceptions, revealing the global
  organization of chromosome
• Gene expression needs the decondensation of
  chromosome loops
• Euchromatin and heterochromatin
• Telomere and centromere are general heterochromatin
• Chromosomes are spatially organized and deposited in
  nucleus
• Mitotic chromosomes are condensed and organized.

				
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posted:10/13/2010
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