Gene and Chromosome

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Gene and Chromosome
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DNA is the genetic material
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Genes and Chromosome

• Molecular Definition of Gene
• the structure and function of DNA
• The global structure of chromosomes
• Organelle DNA

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Molecular Definition of Gene

• The entire nucleic acid sequence that is
  necessary for the synthesis of a functional
  protein and RNA
• Coding region (exon and intron) Regulatory
  sequences (e.g. promotor, enhancer,
  polyadenylation site, splicing sites)
• There are also tRNA and rRNA genes

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Gene Protein
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Baterial Operon and Simple Eukaryotic
Transcription Unit
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Complex Eukaryotic Transcription Complex
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The Structure and Function of DNA

• A DNA molecule consists of two complementary
  chains of nucleotides
• The structure of DNA provides a mechanism for
  heredity

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Structure and Composition of DNA RNA
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Structure and Composition of DNA RNA
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Structure and Composition of DNA RNA
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Structure and Composition of DNA RNA
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The DNA double helix
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DNA is a template for its own duplication
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The Global Structure of Chromosome

• Nucleotides --gt DNA --gt Gene --gt Chromosome --gt
  Genome
• Human DNA is 2 meters long. The nucleus of DNA
  is about 6 µM in diameter.
• Specialized proteins bind to and fold DNA into
  coils and loops, providing higher level of
  organization.
• Although DNA is tightly packed, it can be easily
  accessed by many enzymes that replicate, repair
  or express its genes.

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Nucleus
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A Karyotype of Human Chromosomes
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Normal Aberrant Chromosome
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Organization of Genes on Human Chromosome
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Content of the Human Genome
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Interface / Mitotic Chromosome
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Chromatin Packing
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Nucleosomes
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Structural Organization of the Nucleosome
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Structural Organization of the Nucleosome
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Structural Organization of the Nucleosome
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Organization of the Core Histones
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Organization of the Core Histones
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Organization of the Core Histones
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Chromosome Remodeling

• ATP-driven chromatin remodeling machines change
  nucleosome structure
• Covalent modification of the histone tails can
  profoundly affect chromatin

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Irregularities in Chromatin Structure
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A role Histone H1 in remodeling Chromosome
structure
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Histone Tails
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Mechanism of Chromatin Remodeling Complex
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Cycle of Chromosome Remodeling
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Covalent Modifications of Histone Tails
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Covalent Modifications of Histone Tails
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Heterochromatin/Euchromatin

• There are two types of chromatin in interface,
  heterochromatin and euchromatin
• Heterochromatin is a highly condensed, and
  organized
• 10 of the genome is packed into heterochromatin
• Heterochromatin is resistant to gene expression
• Heterochromatin is concentrated in specific
  regions e.g. centromeres and telomeres

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Organelle DNA

• Mitochondria and Chloroplast DNA
• Exhibit cytoplasmic inheritance
• Encode rRNA, tRNA, and some mitochondrial
  proteins
• Product of mitochondrial genes are not exported
• Mitochondrial gene codes differ from the standard
  nuclear code

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DNA Replication, Repair, and Recombination
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Eukaryotic Cell Cycle
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Eukaryotic Cell Cycle
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DNA Replication

• DNA Polymerase
• Replication Fork
• DNA polymerase - Sliding Ring
• DNA primase - Single-strand binding protein
• DNA helicase
• DNA polymerization in 5-3 direction
• Leading strand
• Lagging strand
• Proofreading mechanisms
• DNA Topoisomerase

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DNA Double Helix is the Template
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Mg2 is required for polymerization
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DNA Polymerase
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DNA replication is semiconservative
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DNA Replication of a Circular Chromosome
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Replication Fork
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Why only 5--gt 3 Direction ?
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Why only 5--gt 3 Direction?For High Fidelity
DNA Synthesis
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Why only 5--gt 3 Direction?For High Fidelity
DNA Synthesis

• 5- 3 Polymerization
• 3- 5 Exonucleolytic Proofreading
• Strand-directed mismatch repair

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Editing by DNA Polymerase
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Exonucleolytic Proofreading by DNA Polymerase
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Exonucleolytic Proofreading by DNA Polymerase
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5- 3 Direction is Energy Efficient
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DNA Synthesis of the Lagging Strand
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RNA Primer Synthesis
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Other Enzymes Proteins in DNA Replication
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DNA Ligase
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Bacterial Replication Fork
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Mammalian Replication Fork
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DNA Helicase
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SSB
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Single-Strand DNA-Binding Protein (SSB)
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Sliding Clamp for DNA polymerase
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Sliding Clamp for DNA polymerase
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Sliding Clamp
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Moving Replication Fork
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Moving Replication Fork
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Mismatch Proofreading Proteins
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DNA Topoisomerase
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Winding Problem
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DNA Topoisomerase I
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DNA Topoisomerase I
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DNA Topoisomerase II DNA Gyrase
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DNA Topoisomerase II
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The Initiation and Completion of DNA Replication
in Chromosome
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DNA Replication in Bacteria
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Refractory period for DNA initiation
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Eukaryotic Chromosome Contains Multiple Origin of
Replication
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Identification of yeast origin of replication
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Eukaryotic Origin of Replication

• Last multisubunit complex(ORC origin recognition
  complex) binds to eukaryotic origin of
  replication
• All yeast Origin of replication has been
  identified (about 150 nucleotide pairs)
• The mammalian origin of replication sequence is
  difficult to identify

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Yeast Origin of Replication
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Telomere
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DNA Repair
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Spontaneous Alterations
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Depurination and Deammination
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Thymine Dimer
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Deamintation
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Depurination
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Double-Strand Break Repair
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DNA Recombination
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Junction
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ssDNA Hybridization
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Rec A in Homologous Recombinaton at DNA Synapsis
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Holiday Junction
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Resolving Holiday Junction
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General Recombination in Mitotic and Meiotic Cells
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Site Specific Recombination

• Moving of mobile genetic elements between
  non-homologous DNA
• Transpositional site-specific recombination
• DNA only transposition
• Cut and Pase transposition
• Replicative transposition
• Retroviral-like retrotransposition
• Nonretroviral retrotransposition
• Conservative site-specific recombination

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Bacterial Transposons
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Cut-and-Paste Transposition
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Replicative Transposon
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Replicative Transposon
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Retrovirus
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Site-specific recombintaion by a retro virus or a
retrovirus-like retrotransposon
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Nonretroviral Retrotransposon
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Conservative site specific recombination
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