The Structure & Function of DNA

1. The Structure & Function of DNA Chapter 10

3. Molecular biology – the study of heredity at the molecular level • All organisms use the same genetic code for translation and transcription and also for replication

4. Biology and Society:Sabotaging HIV • AIDS, acquired immunodeficiency syndrome - one of the most significant health challenges facing the world - infected 40 million worldwide with 3 million deaths - cause of AIDS is infection by the HIV, human immunodeficiency virus - no cure for AIDS but can be slowed by anti-HIV drugs • AZT (azidothymidine), the most effective drug at preventing the spread of HIV - how does AZT stop HIV?

5. AZT and the T Nucleotide • Viruses cannot reproduce on their own – they must infect a host cell - HIV depends on a viral enzyme to convert its RNA genome into a molecule of DNA - the viral enzyme (reverse transcriptase) uses nucleotides (A,T,C,G) from the cytoplasm of the infected cell to build a DNA molecule - AZT is so similar to the T (thymine) nucleotide it can bind to the viral enzyme instead of T (shape and function) - but AZT cannot be incorporated into a growing DNA chain, interferes with the synthesis of HIV DNA

6. Figure 10.1

7. DNA: Structure and Replication • DNA was known to be a chemical in cells by the end of the 19th century - Mendel and other early genetists did all their work without knowledge of DNA • In the late 30s, experimental studies convinced most biologist that a specific molecule was the basis of inheritance - by the 40s scientists knew that chromosomes consisted of 2 types of chemicals: DNA and protein - in the early 50s experimental discoveries had convinced the scientific world that DNA acts as the hereditary material

8. Scientist had identified all its atoms and how they were covalently bonded to one another • Scientist understood the unique properties of DNA - has the capacity to store genetic information - can be copied and passed from generation to generation • What was not understood was the 3-dimensional structure

9. DNA and RNA Structure • Both DNA and RNA are nucleic acids - consist of chains (polymers) of subunits (monomers) called nucleotides - the nucleotides are joined together by covalent bonds between the sugar of one nucleotide and the phosphate of the next (a sugar-phosphate backbone) • The 4 nucleotides found in DNA differ in their nitrogenous bases - thymine (T), cytosine (C), adenine (A), and guanine (G) • RNA has uracil (U) in place of thymine

10. A molecule of DNA contains 2 polynucleotides • Each nucleotide consists of a nitrogenous base, a sugar (blue), and a phosphate group (gold) Figure 10.2

11. The phosphate group with a P atom at its center, is the source of the acid in nucleic acid - the phosphate has given up a hydrogen ion (H+), leaving a negative charge on one of its oxygen atoms • The sugar has 5 carbon atoms: 4 in its ring and one extending above the ring - the ring also includes an oxygen - the sugar is deoxyribose because it is missing an oxygen atom (compared to ribose in RNA) • The nitrogenous base has a ring of nitrogen and carbon atoms with various functional groups - nitrogenous bases are basic

12. Deoxyribonucleic Acid • The 4 nucleotides found in DNA differ only in their nitrogenous bases – there are 2 types - thymine (T) and cytosine (C) are single-ring structures - adenine (A) and guanine (G) are double-ring structures • RNA – ribonucleic acid - has the nitrogenous base uracil (U) instead of T - contains ribose instead of deoxyribose

13. Watson and Crick used X-ray crystallography data from Rosalind Franklin to reveal the basic DNA shape • While in John Randall’s lab Franklin had discovered that DNA could crystallize into two different forms, an A and a B form Fig 10.3b

14. Watson and Crick are shown in 1953 with their model of the double helix • In 1962 Watson, Crick, and Wilkins received the Nobel Prize for their work Figure 10.3a

15. A rope-ladder model of a double-helix. The ropes at the sides represent the sugar-phosphate backbones. • Each wooden rung stands for a pair of bases connected by H bonds Fig 10.4

16. Bases pair in a complementary fashion • Bases hydrogen bond to each other • DNA strands in a double helix are antiparallel – the 2 sugar-phosphate backbones are oriented in opposite directions Fig 10.5

17. DNA Replication • When a cell or whole organism reproduces, a complete set of genetic instructions must pass from one generation to the next • Watson and Crick’s model for DNA suggested that DNA replicates by a template mechanism - each DNA strand serves as a mold or template, to guide reproduction of the other strand - if you know the sequence of bases in one strand of the double helix, you can determine the sequence of bases in the other strand by applying the base-pairing rules

18. The 2 strands of the original (parental) DNA molecule (blue) serve as templates for making new (daughter) strands (orange) • Replication results in 2 daughter DNA molecules, each consisting of one old strand and one new strand • The parental DNA untwists as its strands separate, and the daughter DNA rewinds as it forms Figure 10.6

19. DNA Replication • The nucleotides are lined up one at a time along the template strand in accordance with the base-pairing rules - enzymes link nucleotides to form the new DNA strands - the completed new molecules, identical to the parental molecule, are known as daughter DNA molecules • DNA polymerases – enzymes that make the covalent bonds between the nucleotides of a new DNA strand - as an incoming nucleotide base-pairs with its complement on the template strand, a DNA polymerase adds it to the end of the daughter strand

20. DNA replication proceeds at a rate of 50 nucleotides per second - only about one in a billion incorrectly pair • DNA polymerases and some associated proteins are also involved in repairing damaged DNA - DNA can be damaged by toxic chemicals, by high-energy radiations such as X-rays and ultraviolet light

21. Damage to DNA by UV Light • The UV radiation in sunlight can damage the DNA in skin cells • Fortunately, cells can repair some of the damage – use some of the same enzymes that catalyze the replication of DNA • Protect your skin - use sunscreen and protective clothing Fig 10.7

22. DNA replication begins at specific sites or origins of replication on a double helix - proceeds, creating replication ‘bubbles’ - parental DNA strands open up as daughter strands elongate on both sides of each bubble - a DNA molecule of a eukaryotic chromosome has many origins where replication can start simultaneously - eventually all the bubbles merge, yielding 2 completed double-stranded daughter DNA molecules • DNA replication ensures that all the body (somatic) cells carry the same genetic information - also the means by which genetic information is passed along to offspring

23. Figure 10.8

24. Checkpoint • Compare and contrast the chemical components of DNA and RNA • Along one strand of a DNA double helix is the nucleotide sequence AAGTGTAAC. What is the sequence for the other DNA strand? • How doe complementary base pairing make the replication of DNA possible? • What is the function of DNA polymerase in DNA replication?

25. Answers • Both are polymers of nucleotides; a nucleotide consists of a sugar + a nitrogenous base + a phosphate group. In RNA the sugar is ribose, in DNA the sugar is deoxyribose. RNA uses uracil (U) and DNA thymine (T) • AAGTGTAAC = TTCACATTG • When the 2 strands of the double helix separate, each serves as a template – complementary strands • This enzyme convalently connects nucleotides one at a time to one end of a growing daughter strand as the nucleotides line up along a template strand according to the base-pairing rules

26. The Flow of Genetic Information from DNA to RNA to Proteins • How does DNA function as the inherited directions for a cell or organism? • What are the instructions and how are these instructions carried out?

27. How an Organism’s Genotype Produces Its Phenotype • An organism’s genotype, its genetic makeup, is the sequence of nucleotide bases in its DNA • The phenotype is the organism’s specific traits - arise from the actions of a wide variety of proteins - examples include enzymes that catalyze metabolic reactions and structural proteins that provide the infrastructure for the body of an organism

28. DNA specifies the synthesis of proteins – but a gene cannot build a protein directly - dispatches instructions in the form of RNA (mRNA) - mRNA programs protein synthesis - molecular ‘chain of command’ is from DNA in the nucleus to RNA to protein synthesis in the cytoplasm • The 2 main stages are: - Transcription, the transfer of genetic information from DNA into an RNA molecule - Translation, the transfer of the information in the RNA into a protein

29. Relationship between genes and enzymes came in the 40s - from the work of George Beadle and Edward Tatum with the orange bread mold Neurospora crassa - studied strains of the mold that were unable to grow on the usual growth medium - these strains lacked an enzyme in a metabolic pathway that produced a molecule the mold needed - they were able to show that each mutant was defective in a single gene

30. Beadle and Tatum hypothesis: ‘one gene-one enzyme • Has since been modified to include all types of proteins: The one gene – one polypeptide hypothesis states that the function of an individual gene is to dictate the production of a specific polypeptid ’

31. Figure 10.9

32. From Nucleotides to Amino Acids: An Overview • Genetic information in DNA is transcribed into RNA then translated into polypeptides - how is the chemical language of DNA translated into the different Chemical language of polypeptides? • Both DNA and RNA are polymers of nucleotides strung together in specific sequences that convey information - specific sequences of bases each with a beginning and an end, make up the genes on a DNA strand - a typical gene consists of 1000s of nucleotides and a single DNA molecule may contain 1000s of genes

33. A segment of DNA is transcribed into an RNA molecule - the process is called transcription because the nucleic acid language of DNA has been rewritten into RNA - RNA was synthesized using the DNA strand as a template, the nucleotide bases of the RNA molecule are complementary to those on the DNA strand • Translation is the conversion of the nucleic acid language to a polypeptide language - the monomers of polypeptides are the 20 amino acids common to all organisms - the message is written in a linear sequence of mRNA - sequence of nucleotides of the RNA molecule dictates the sequence of amino acids

34. Rules for translation of a RNA message into a polypeptide - there are only 4 different kinds of nucleotides in DNA (A,G,C,T) and RNA (A,G,C,U) - if each nucleotide base coded for one amino acid, only 4 amino acids could be constructed - triplets of bases or codons are the smallest ‘words’ that can specify all the amino acids - 43 = 64 possible code words (more than 20) - redundancy of the code, more than one codon can code for an amino acid • One DNA codon (3 nucleotides)  one RNA codon (3 nucleotides)  one amino acid

35. A segment from a strand of gene 3 - sequence of bases • The red strand represents the results of transcription: an RNA molecule – its base sequence is complementary to that of the DNA • The purple chain represents the results of translation: a polypeptide Brackets indicate that 3 RNA nucleotides (a codon) code for each amino acid Figure 10.10

36. Figure 10.11