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DNA—the thread of life Biol 100 – K.Marr

DNA—the thread of life Biol 100 – K.Marr. Topics this lecture DNA structure and Replication Chapter 10 in Essential Biology by Campbell et al Lab 7. Modeling DNA Structure, DNA Replication and Protein Synthesis Read the introduction carefully

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DNA—the thread of life Biol 100 – K.Marr

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  1. DNA—the thread of lifeBiol 100 – K.Marr • Topics this lecture • DNA structure and Replication • Chapter 10 in Essential Biology by Campbell et al • Lab 7.Modeling DNA Structure, DNA Replication and Protein Synthesis Read the introduction carefully • This week: Part 1 (through page 9)—modeling DNA Structure and Replication • Next week: Part 2—modeling transcription and translation

  2. Outline for Next few Lectures Chapter 10—Molecular Biology of the Gene • Cystic Fibrosis Case Study • Central Dogma of Biology • Structure of DNA • Replication of DNA • Protein Synthesis • Transcription = Reading of DNA to make RNA • Translation = Reading of mRNA by ribosomes to make protein Chapter 12—DNA Technology • Application of Gene Therapy and biotechnology to cystic fibrosis

  3. Cystic fibrosis—a genetic disease • View GATTACA trailer • View Cystic Fibrosis Case Study Movie • available @ lecture page of class website • Optional Reading • Cystic Fibrosis Foundation Website: http://www.cff.org • Welsh, M.J. and A.E. Smith. Cystic fibrosis. Scientific American, December 1995

  4. Symptoms of CF Mucus-clogged Airways; Severe Respiratory infections Salty sweat due to altered salt secretion in sweat ducts Problems with digestion due to clogged duct from pancreas Lung Pancreas Infertilty in males due to clogged sex ducts Testis Cell lining ducts of the body

  5. Cystic Fibrosis: autosomal recessive Most common lethal genetic disease • 1 in 2000 children is born with CF in U.S. • Untreated children die by age 5 • Ave. life expectancy: ~27 yrs • Special diet + daily dose of antibiotic prevent infection Carriers of CF gene: • Hispanics: 1 in 46 • African Americans: 1 in 63 • Asian Americans: 1 in 150 • Caucasian of European descent: 1 in 25 • CF allele protects against the plague and many viruses

  6. Cystic Fibrosis • A single faulty protein is connected to the symptoms • In 1989 the gene was mapped to chromosome #7

  7. Our Goal • To determine the connection between the symptoms associated with cystic fibrosis and DNA • Let’s revisit the central dogma of biology…

  8. Central Dogma of Biology • Genes interacting with their environment determine the phenotype of an Organism

  9. Central Dogma of Biology • DNA specifies the synthesis of proteins in two stages • Transcription____________________________________ • Translation______________________________________ • Let’s learn a bit about the structure of DNA DNA Nucleus Transcription RNA Cytoplasm Translation Protein

  10. DNA Structure • Consists of 2 strands joined together by weak hydrogen bonds • Rungs of the ladder are hydrogen bonded N-bases • View Animation of DNA & RNA Structure DNA is like a rope ladder twisted into a spiral Twist

  11. DNA and RNA: Polymers of Nucleotides • Nucleotide: base + sugar + phosphate • Note carbon numbers on sugar • Nucleotides join to form a sugar-phosphate backbone

  12. Nitrogen Bases found in DNA & RNA • Uracil replaces thymine in RNA

  13. Representation of one Strand of DNA 5’ end Phosphate group Nitrogenous base Sugar Nitrogenous base (A,G,C, or T) Nucleotide Thymine (T) Phosphategroup Sugar (deoxyribose) 3’ end DNA nucleotide Polynucleotide Sugar-phosphate backbone

  14. DNA Structure • Complementary pairing of bases A to T and G to C • Note 5’ and 3’ ends of each strand

  15. It’s in the genes... • What’s a gene? • Sequence of DNA bases on a chromosome that determines the amino acid sequence of a protein • The kind of proteins an organism makes helps to determine it’s phenotype • Genes are... • copied during __ S-phase of the cell cycle (DNA replication)_____ • passed to offspring __during fertilization and when cells divide__ • Genes can change or mutate—how? • View animation of DNA Replication • available at the lecture section of class website

  16. DNA Replication(simplified) One DNA molecule before replication 5’ 3’ Nucleus Parental strands Separated by Helicase 5’ 3’ 5’ 3’ DNA polymerase Free nucleotides diffuse in and pair up with bases on the Separated strands— A with T, G with G 5’ 3’ Parent strands conserved DNA polymerase joins together the newly aligned nucleotides New strands formed 3’ 5’ 5’ 3’ After Replication: 2 Identical DNA molecules (sister chromatids) 3’ 3’ 5’ 5’

  17. DNA Replication:DNA polymerase can only add nucleotides to the 3’ end of another nucleotide(slide 1 of 2) a.) Primer binding b.) Synthesis begins Two strands of the parental DNA molecule Replication fork moves DNA polymerase and other enzymes Replication fork 3’ end 5’ end Primer (5’ end) Newly made strands

  18. c.) Replication continues d.) Replication complete DNA Replication(slide 1 of 2) Replication fork moves This strand is synthesized continuously toward the fork Two identical daughter DNA molecules This strand is made by discontinuous synthesis: Fragments are synthesized and then joined together

  19. DNA replication Self-test Questions • When during the cell cycle does it occur? • What do we start with? • What do we end with? • Where in a cell does DNA replication occur? • What’s needed for DNA replication to occur? • What is the sequence of events? • Why is DNA replication said to be semi-conservative? • What does proofreading mean in terms of DNA replication? • What does the proofreading during DNA replication?

  20. How do nucleotide analogues work to stop DNA replication in cancer cells and HIV?The drug AZT, below, is effective at preventing the spread of HIV. How? Thymine (T) Part of a Thymine nucleotide AZT

  21. DNA can be damaged by ultraviolet light • Enzymes (e.g. DNA polymerase) can repair the damage. • Is the damage always repaired? Consequences? • Why does burnt skin peel? What gene is involved? • Role of Apoptosis? • Role of p53 gene? • Advantages of peeling? • Disadvantages?

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