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THE MOLECULAR BASIS OF INHERITANCE
Chapter 16
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THE SEARCH FOR GENETIC MATERIAL
Frederick Griffith (1928) something changed normal cells into pneumonia causing cells in mice Alfred Hershey & Martha Chase (1952) DNA of virus injected into bacteria, not protein
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Figure 16.1 Transformation of bacteria
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Figure 16.2a The Hershey-Chase experiment: phages
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Figure 16.2ax Phages
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Figure 16.2b The Hershey-Chase experiment
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Erwin Chargaff (1947) Amounts of G = C and A = T in DNA Rosalind Franklin (1950’s) Photographed DNA using X-ray crystallography James Watson and Francis Crick (1953) DNA is a double helix with base pairs as the rungs
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Figure 16.4 Rosalind Franklin and her X-ray diffraction photo of DNA
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Figure 16.3 The structure of a DNA stand
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Figure 16.0 Watson and Crick
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DNA STRUCTURE 4 Bases Purines: adenine and guanine
Pyrimidine: cytosine and thymine A – T and C – G Hydrogen bonds connect the base pairs to make the rungs Deoxyribose and phosphate make up the uprights Nucleotide – a base, a sugar, and a phosphate
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Purine and pyridimine
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Figure 16.6 Base pairing in DNA
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Figure 16.5 The double helix
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SEMICONSERVATIVE MODEL OF REPLICATION
When DNA copies itself, the resulting “copy” is one of the original strands with a new strand
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Figure 16.7 A model for DNA replication: the basic concept
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Figure 16.7 A model for DNA replication: the basic concept
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Figure 16.8 Three alternative models of DNA replication
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Figure 16.9 The Meselson-Stahl experiment tested three models of DNA replication (Layer 1)
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Figure 16.9 The Meselson-Stahl experiment tested three models of DNA replication (Layer 2)
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Figure 16.9 The Meselson-Stahl experiment tested three models of DNA replication (Layer 3)
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Figure 16.9 The Meselson-Stahl experiment tested three models of DNA replication (Layer 4)
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Figure 16.10 Origins of replication in eukaryotes
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DNA REPLICATION Origins of replication – specific sequences of nucleotides that initiate replication Replication fork – a Y shaped region where new nucleotides are added DNA polymerases – enzymes that break H bonds (unwind helix) and add complementary nucleotides Reaction driven by nucleoside triphosphates (like ATP) Loose 2 phosphate groups to be added as a nucleotide
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Figure 16.11 Incorporation of a nucleotide into a DNA strand
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The 2 strands of a double helix are antiparallel
The sugar-phosphate backbones run in opposite directions One is 5’ to 3’ while other is 3’ to 5’ #1 is the C attached to a base and #5 is the C attached to phosphate
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Figure 16.12 The two strands of DNA are antiparallel
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DNA polymerases can only attach nucleotides to the free 3’ end of existing an polynucleotide (already paired to complementary strand). DNA polymerases add nucleotides in only the 5’ to 3’ direction Leading strand – made by DNA polymerase following replication fork
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Figure 16.13 Synthesis of leading and lagging strands during DNA replication
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The other strand of DNA that is made is called the lagging strand
Polymerase makes a short strand As bubble grows, more short strands are made called Okazaki fragments
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Figure 16.14 Priming DNA synthesis with RNA
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Okazaki fragments are joined by DNA ligase
Priming: polymerase must attach nucleotides to an existing polynucleotide at a 3’ end Primase (an enzyme) adds RNA nucleotides to make a primer ~10 bases long
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Polymerase can then add its complementary nucleotides
Polymerase also replaces certain RNA nucleotides of primer For lagging strand each fragment must be primed, but only one primer is needed for entire leading strand
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DNA Polymerases DNA polymerase I – removes primers from 5’ end of leading strand and each Okazaki fragment and replaces it with DNA nucleotides DNA polymerase III – adds nucleotides to both leading and lagging strand
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OTHER ENZYMES… Helicase – untwists helix at replication fork Topoisomerase – relieves the strain that untwisting causes ahead of the replication fork Single-strand binding protein – hold strands apart while replication occurs
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Figure 16.15 The main proteins of DNA replication and their functions
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Figure 16.16 A summary of DNA replication
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PROOFREADING Mismatch repairing – polymerase checks each addition Excision pair – nuclease cuts out bad section of strand
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Figure 16.17 Nucleotide excision repair of DNA damage
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Figure 16.18 The end-replication problem
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TELOMERES Impossible on lagging strand to copy the end of 5’ strand
This leaves a gap that would shorten DNA every time it replicates Telomeres (TTAGGG) repeated many times protects genes by postponing erosion of genes from this shortening effect Telomerase – lengthens telomeres Contains an RNA sequence that is the template for a telomere Present in germ cells (for future gametes) Increased activity in cancer cells (allows for more cell division)
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Figure 16.19a Telomeres and telomerase: Telomeres of mouse chromosomes
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