1. The Structure and Function of Macromolecules
Chapter 5
2 – Nucleic Acids

2. Macromolecules: The Molecules of Life
Carbohydrates
Nucleic Acids
Proteins
Lipids

3. The Structure of Nucleic Acid Monomers
Nucleotide -- nitrogenous base, a pentose sugar, and a phosphate group
Nucleoside -- portion of a nucleotide without the phosphate group

4. FIGURE 3-24 Deoxyribose nucleotide

5. Nucleotide Monomers There are two families of nitrogenous bases:
Pyrimidines have a single six-membered ring
Purines have a six-membered ring fused to a five-membered ring

6. Nitrogenous base Phosphate group Pentose sugar
Nitrogenous bases
Pyrimidines
Purines
Pentose sugars
Cytosine C
Thymine (in DNA) T
Uracil (in RNA) U
Adenine A
Guanine G
Deoxyribose (in DNA)
Nucleoside components
Ribose (in RNA)
5¢ end
3¢ end
Nucleoside
Nitrogenous
base
Phosphate
group
Nucleotide
Polynucleotide, or
nucleic acid
Pentose
sugar

7. Purines vs Pyrimidines
King CUT lives in a Pyramid!
CUT = Cytosine, Uracil, Thymine
Cytosine, Uracil, Thymine are Pyrimidines
Pyrimidines are CUT from Purines
Pyrimidines are single-ring compounds, Purines are double ring compounds

8. Non-polymer Nucleotides
not large molecules or polymers
Intracellular messengers
Energy carriers
Enzyme assistants

9. Other Nucleotides Nucleotides as intracellular messengers
Cyclic nucleotides (e.g. cyclic AMP) carry chemical signals between molecule

10. Other Nucleotides Nucleotides as energy carriers
Adenosine triphosphate (ATP) carries energy stored in bonds between phosphate groups

11. NAD+: Nicotinamide Adenine Dinucleotide
Vitamin B3

12. NADP+: Nicotinamide Adenine Dinucleotide Phosphate

13. FAD: Flavin Adenine Dinucleotide

14. Other Nucleotides Nucleotides as enzyme assistants
Coenzymes help enzymes promote and guide chemical reactions

15. Nucleotide Polymers Nucleotide monomers – build polynucleotide
Covalent bonds
–OH group on the 3´ carbon of one nucleotide
phosphate on the 5´ carbon on the next
Backbone of sugar-phosphate units
nitrogenous bases as appendages

16. LE 5-26a Nucleoside Nitrogenous base Phosphate group Pentose sugar
5¢ end
Nucleoside
Nitrogenous
base
Phosphate
group
Pentose
sugar
Nucleotide
3¢ end
Polynucleotide, or
nucleic acid

17. Nucleotide Polymers DNA antiparallel Two types: DNA makes more DNA
Deoxyribonucleic acid (DNA)
Ribonucleic acid (RNA)
DNA antiparallel
Backbones in opposite 5´ to 3´ directions
DNA makes more DNA
DNA directs synthesis of messenger RNA (mRNA)
mRNA controls protein synthesis
Occurs in ribosomes

18. DNA vs RNA Pyrimidine in DNA is Thymine; RNA uracil
DNA is double-stranded; RNA single
In DNA, the sugar is deoxyribose; in RNA ribose
Pyrimidine in DNA is Thymine; RNA uracil
DNA directs hereditary information; RNA directs protein synthesis
DNA is DNA; RNA comes in 3 forms
messenger RNA (mRNA)– protein structure from DNA to ribosome
ribosomal RNA (rRNA) – makes up ribosomes
transfer RNA (tRNA) – carries amino acids to the ribosome/mRNA

19. Types of RNA DNA is DNA; RNA comes in 3 forms …. not exactly!
messenger RNA (mRNA)– protein structure from DNA to ribosome
ribosomal RNA (rRNA) – makes up ribosomes
transfer RNA (tRNA) – carries amino acids to the ribosome/mRNA
…. not exactly!

20. DNA Most celebrated molecule of our time Hereditary information
Sugar–phosphate
backbone
5 end
Nitrogenous
bases
Thymine (T)
Adenine (A)
Cytosine (C)
DNA nucleotide
Phosphate
3 end
Guanine (G)
Sugar (deoxyribose)
DNA
Most celebrated molecule of our time
Hereditary information
Directs the development of biochemical, anatomical, physiological, and (to some extent) behavioral traits

21. Variation and Diversity
Slight differences between closely related individuals
Distantly related individuals – greater differences
© 2009 W.W. Norton & Company, Inc. DISCOVER BIOLOGY 4/e

22. The Search for Genetic Material
It needed to:
Contain information
Be easy to copy
Be variable, to account for diversity

23. DNA or Protein? Nucleic Acids Proteins
First isolated Friedrich Miescher
Proteins
Recognized in 18th C.
First described -- Gerardus Johannes Mulder
Named -- Jöns Jacob Berzelius in 1838.

24. DNA or Protein? Thomas Hunt Morgan – 1911
Chromosomes carried genes
Composed of DNA and protein
Which is the genetic material?
Protein is large, complex, and stores info
DNA seemed too small and unlikely

25. Griffith Experiment -- 1928
Transformation of one strain by another
Two strains of bacteria
R—harmless
S—deadly
Heat‑killed S is also harmless
Heat‑killed S makes R deadly

26. Avery, MacLeod, & McCarty 1944
Used the same assay system
Isolated compounds from Strain S
Added these to Strain R
Only DNA transformed Strain R

27. Additional Evidence
Erwin Chargaff: DNA composition varies from one species to the next
Makes DNA more credible
By 1950s -- DNA composition known but not structure

28. Hershey and Chase -- 1952 Phage head Tail Tail fiber 100 nm DNA
LE 16-3
Hershey and Chase
Phage
head
Tail
Tail fiber
100 nm
DNA
Bacterial cell

29. Hershey and Chase
DNA, not protein, is genetic material

30. Franklin’s X-ray diffraction photograph of DNA
LE 16-6
Rosalind Franklin
Franklin’s X-ray diffraction
photograph of DNA

31. Watson & Crick Determined the 3D structure of DNA
Structure revealed its function
Franklin’s X-ray crystallographic studies
Double helix
Ladder twisted into a spiral coil
Uniform diameter

32. Purine + purine: too wide
LE 16-UN298
Purine + purine: too wide
Pyrimidine + pyrimidine: too narrow
Purine + pyrimidine: width
consistent with X-ray data

33. Base-Pairing Rules Strands held together by hydrogen bonds
Strict base-pairing rules followed
Purine to Pyrimidine
A binds to T
G binds to C
Makes copying sequence possible

35. LE 5-27 5¢ end 3¢ end Sugar-phosphate backbone Base pair (joined by
hydrogen bonding)
Old strands
Nucleotide
about to be
added to a
new strand
5¢ end
New
strands
3¢ end
5¢ end
5¢ end
3¢ end

36. FIGURE 9-6 Basic features of DNA replication
During replication, the two strands of the parental DNA double helix separate. Free nucleotides that are complementary to those in each strand are joined to make new daughter strands. Each parental strand and its new daughter strand then form a new double helix.

37. DNA Structure Explains Function
Easily copied
Each strand is a template for the other
DNA sequence is information
Information contained in the order of the four bases
Millions of bases in length
Accounts for diversity
Alleles have different DNA sequences

38. Replication Models Meselson & Stahl (1958)
Conservative model. The two parental strands reassociate after acting as templates for new strands, thus restoring the parental double helix.
Semiconservative model. The two strands of the parental
molecule
separate, and each functions as a template for synthesis of a new, comple-mentary strand.
Dispersive model. Each strand of both daughter molecules contains
a mixture of
old and newly synthesized
DNA.
Parent cell
First
replication
Second
Replication Models
Meselson & Stahl (1958)
Labeled strand -- heavy isotope of nitrogen
Labeled free nucleotides -- lighter isotope of nitrogen

39. LE 16-11 Bacteria cultured in medium containing 15N Bacteria
transferred to
medium
containing
14N
DNA sample
centrifuged
after 20 min
(after first
replication)
DNA sample
centrifuged
after 40 min
(after second
replication)
Less
dense
More
dense
First replication
Second replication
Conservative
model
Semiconservative
model
Dispersive
model

40. DNA Replication: A Closer Look
Quick and accurate
More than a dozen enzymes and other proteins participate

41. Replication Origins of Replication
Eukaryotic chromosome -- hundreds to thousands
Replication proceeds in both directions
Replication fork – ends of each replication bubble

42. LE 16-12 Parental (template) strand 0.25 µm Origin of replication
Daughter (new) strand
Bubble
Replication fork
Two daughter DNA molecules
In eukaryotes, DNA replication begins at may sites
along the giant DNA molecule of each chromosome.
In this micrograph, three replication
bubbles are visible along the DNA
of a cultured Chinese hamster cell
(TEM).

43. DNA Replication DNA Polymerase Many enzymes and proteins are involved
Catalyze elongation at a replication fork
Many enzymes and proteins are involved
Initiate replication
Unwind the DNA
Stabilize the open strands
Connect bases -- nucleoside triphosphate
Process takes about 8 hours in humans

44. LE 16-13 New strand Template strand 5¢ end 3¢ end 5¢ end 3¢ end Sugar
Base
Phosphate
DNA polymerase
3¢ end
3¢ end
Pyrophosphate
Nucleoside
triphosphate
5¢ end
5¢ end

45. Antiparallel Elongation
The antiparallel structure of the double helix (two strands oriented in opposite directions) affects replication
DNA polymerases add nucleotides only to the free 3end of a growing strand
DNA elongates
only in the 5 to 
3direction

46. The DNA Replication Machine
Complex -- probably stationary
DNA polymerase
“reels in” parental DNA
“extrude” daughter DNA