Chapter 1 DNA Structure

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Chapter 1DNA Structure Gene Expression

• Structure of DNA, RNA, and polypeptides
• DNA RNA are long polymers of nucleotides
• - nitrogenous bases purines, pyrimidines
• - differences between DNA RNA
• - difference between nucleoside and nucleotide

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• Polypeptides are long polymers of amino acids
• - structure of amino acids charged polar
  (basic and acidic), uncharged polar, and nonpolar
  (hydrophobic).

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• 2. Chemical bonds and structure Primary linear
  structure of DNA, RNA, and proteins is held by
  strong covalent bonds while weaker noncovalent
  bonds (hydrogen, ionic, Van der Waals, and
  hydrophobic forces) are responsible for
  intermolecular associations in the secondary,
  tertiary, and in some cases (proteins) quaternary
  structure of the molecule.

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• 3. DNA structure and its replication
• DNA is an antiparallel double helix

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• Intramolecular hydrogen bonding permits RNA-DNA
  duplexes and double-stranded RNA formation. Such
  structure formations are relevant in regulating
  gene expression.

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• DNA replication is semi-conservative

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• DNA replication in mammalian cells requires
  several enzymes and other proteins
  Topoisomerases, helicases, DNA-directed DNA
  polymerase, RNA-directed DNA polymerases (reverse
  transcriptase) such as that present in telomerase
  (used to replicates ends of chromosomes). See
  Box 1.2 (page 12).

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• Viral genomes are frequently maintained by RNA
  replication.

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• 4. RNA transcription gene expression
• DNA ? RNA ? Protein (in most cases)
• Only a small fraction is expressed to give
  proteins or just RNA.
• For any gene, there is a sense strand (like the
  RNA transcript) and a template strand (antisense
  strand).

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• Eukaryotic gene expression requires cis-acting
  regulatory elements (DNA sequences such as
  promoters, 5 UTR, 3UTR, enhnacers, silencers)
  and transacting transcription factors (proteins
  such as activators and repressors of gene
  expression.

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• Housekeeping genes (such as those encoding
  histones and ribosomal proteins) are
  constitutively expressed in all cell types.
• Tissue-specific genes are spatially regulated
  while developmentally regulated genes are
  spatially regulated.
• Transcriptionally inactive chromatin is
  characterized by being heterochromatic (highly
  condensed), is tightly bound to H1 histones, and
  is replicated in late S phase.
• Transcriptionally active chromatin is euchromatic
  (open conformation), replicated early in S phase,
  weak binding to H1 histone, and has extensive
  acetylation of the histones H2A, H2B, H3, and
  H4).

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• 5. RNA processing
• RNA splicing (spliceosome)
• Capping by 7-methylguanosine at 5 end
• Polyadenylation for mRNA the sequence AAUAAA
  at 3 end is a polyadenylation signal and
  cleavage occurs 15-30 nucleotides downstream from
  such signal. Poly(A) polymerase then adds about
  200 adenylate residues forming a poly(A) tail.

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• 6. Translation, post-transcriptional processing
  and protein structure
• 5UTR and 3UTR regions of the mRNA are not
  translated.
• The genetic code is degenerate (wobble hypothesis
  at the third base position of codons) and not
  quite universal.

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• Post-translational modification include chemical
  modifications of some amino acids and polypeptide
  cleavage.
• By adding carbohydrate groups (N-glycosylation
  O-glycosylation)
• By addition of lipid groups (glycosylphosphatidyl
  inositol)
• Postranslational cleavage e.g. insulin.
• Protein secretion and intracellular export.

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