OBJECTIVES OF THE COURSE for section 3 and 4:Molecules of Life: BiomoleculesDNA and the gene:DNA’s Primary StructureDNA’s Secondary StructureSlide 6DNA Strands Are Templates for DNA SynthesisHow Do the Old and New DNA Strands Interact?The Meselson-Stahl ExperimentSlide 10Slide 11A Comprehensive Model for DNA SynthesisCharacteristics of DNA PolymerasesSlide 14How Does Replication Get Started?Slide 16How Is the Helix Opened and Stabilized?How Is the Leading Strand Synthesized?Slide 19The Lagging StrandHow Is the Lagging Strand Synthesized?The Discontinuous Replication HypothesisThe Discovery of Okazaki FragmentsSlide 24Slide 25Slide 26DNA Synthesis Enzymes Are Well-OrganizedDNA replication requires many proteins: Function of each??Proteins Involved in DNA Synthesis – table 14.1Describe the roles and relationships of all the following enzymes and structures in replication:Replicating the Ends of Linear ChromosomesSlide 32Slide 33Slide 34Replication in Somatic CellsRepairing Mistakes and DamageSlide 37Slide 38How Does DNA Polymerase Proofread?Slide 40Repairing Damaged DNAXeroderma Pigmentosum: A Case StudySlide 43Slide 44DNA Repair Genes and CancerCancer Treatments -How do cancer treatments work?Slide 47ChemotherapySlide 49Slide 50How Does Information Flow from Genes to Proteins?© 2011 Pearson Education, Inc.OBJECTIVES OF THE COURSE for section 3 and 4: •Heredity and the genome: Cell cycle and cell division •Understand the structure and synthesis of nucleic acids and proteins. Molecular basis of genetics and regulation of gene expression. •Mutations, Defective proteins and Diseases•Genetic engineering- biotechnology in agriculture and in medicine© 2011 Pearson Education, Inc.Molecules of Life: BiomoleculesProteins: Building blocks of proteins are the amino acids (C, H, O, N) (monomer = amino acid)example: enzymes catalyzing biochemical reactions, antibodies protecting against diseases… Nucleic acids: RNA, DNA (C, H,O, P, N) Storing/ transferring genetic information (monomer = nucleotide)Carbohydrates: Monosaccharides & derivatives (C, H, O) Cn(H2O)n (monomer = monosaccharide)example: Starch, cellulose…(phosphorylated / sulphated sugars)lipids: Fatty acids, Cholesterol (C,H,[O]) membrane components (phosphorylated lipids)© 2011 Pearson Education, Inc.DNA is an informational molecule: information is encoded in the sequences of bases.RNA uses the information to determine the sequence of amino acids in proteins.•PROTEINS and DNA/RNA: These are two cellular components with the Proteins being the executors of the cell’s specific functions while DNA is the repository of the information needed to produce proteins. •FLOW OF BIOLOGICAL INFORMATION: DNA  RNA  POLYPEPTIDE (protein) STRUCTURE / FUNCTIONDNA and the gene:© 2011 Pearson Education, Inc.DNA’s Primary Structure •The primary structure of DNA has two major components:1. A backbone made up of the sugar and phosphate groups of deoxyribonucleotides.2. A series of nitrogen-containing bases that project from the backbone.DNA has directionality—one end has an exposed hydroxyl group on the 3′ carbon of deoxyribose, and the other end has an exposed phosphate group on a 5′ carbon.The molecule thus has a 3′ end and a 5′ end.© 2011 Pearson Education, Inc.DNA’s Secondary Structure•Watson and Crick proposed that two DNA strands line up in the opposite direction to each other, in what is called antiparallel fashion.•The antiparallel strands twist to form a double helix.•The secondary structure is stabilized by complementary base pairing:–Adenine (A) hydrogen bonds with thymine (T).–Guanine (G) hydrogen bonds with cytosine (C).© 2011 Pearson Education, Inc.© 2011 Pearson Education, Inc.DNA Strands Are Templates for DNA SynthesisWatson and Crick suggested that the existing strands of DNA served as a template (pattern) for the production of new strands, with bases being added to the new strands according to complementary base pairing.•Biologists then proposed three alternative hypotheses for how the old and new DNA strands interacted during replication:–Semiconservative replication.–Conservative replication.–Dispersive replication.© 2011 Pearson Education, Inc.How Do the Old and New DNA Strands Interact?•In semiconservative replication, the parental DNA strands separate and each is used as a template for the synthesis of a new strand. Daughter molecules each consist of one old and one new strand.•In conservative replication, the parental molecule serves as a template for the synthesis of an entirely new molecule.•In dispersive replication, the parent molecule is cut into sections such that the daughter molecules contain old DNA interspersed with newly synthesized DNA.© 2011 Pearson Education, Inc.The Meselson-Stahl Experiment•Meselson and Stahl designed an experiment to provide more information about whether one of these hypotheses was correct. •They grew E. coli in the presence of “heavy” nitrogen (15N) to label the bacteria's DNA. After many generations, they moved the bacteria to a normal 14N-containing medium and separated the DNA by density.•The densities of the resulting DNA samples supported semiconservative DNA replication as the mechanism by which the hereditary material is duplicated.© 2011 Pearson Education, Inc.© 2011 Pearson Education, Inc.© 2011 Pearson Education, Inc.A Comprehensive Model for DNA Synthesis•Meselson and Stahl showed that each parental DNA strand is copied in its entirety, but did not illustrate a mechanism for this process.•The discovery of DNA polymerase, the enzyme that catalyzes DNA synthesis, cleared the way for understanding DNA replication reactions.© 2011 Pearson Education, Inc.Characteristics of DNA Polymerases •A critical characteristic of DNA polymerases is that they can only work in one direction.DNA polymerases can add deoxyribonucleotides to only the 3′ end of a growing DNA chain. As a result, DNA synthesis always proceeds in the 5′ → 3′ direction.•DNA polymerization is exergonic because the monomers that act as substrates in the reaction are deoxyribonucleoside triphosphates (dNTPs), which have high potential energy because of their three closely packed phosphate groups.© 2011 Pearson Education, Inc.© 2011 Pearson Education, Inc.How Does Replication Get Started?•In bacterial chromosomes, the replication process begins at a single location, the origin of