Download 07 NucleicAcids-06b

The Structure and
Function of
Macromolecules
Chapter 5
2 – Nucleic Acids
Macromolecules:
The Molecules of Life
 Carbohydrates
 Nucleic Acids
 Proteins
 Lipids
2
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
3
4
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
5
5 end
Nitrogenous bases
Pyrimidines
Cytosine
C
Nucleoside
Thymine (in DNA) Uracil (in RNA)
U
T
Nitrogenous
base
Purines
Adenine
A
Guanine
G
Phosphate
group
Pentose sugars
Nucleotide
3 end
Deoxyribose (in DNA)
Nucleoside components
Ribose (in RNA)
Polynucleotide, or
nucleic acid
Pentose
sugar
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
7
Non-polymer Nucleotides
 not large molecules or polymers
 Intracellular messengers
 Energy carriers
 Enzyme assistants
8
Other Nucleotides
Nucleotides as intracellular messengers

Cyclic nucleotides (e.g. cyclic AMP) carry chemical
signals between molecule
9
Other Nucleotides
 Nucleotides as energy carriers
 Adenosine triphosphate (ATP) carries energy stored
in bonds between phosphate groups
10
NAD+: Nicotinamide Adenine Dinucleotide
Vitamin B3
11
NADP+: Nicotinamide Adenine Dinucleotide Phosphate
12
FAD: Flavin Adenine Dinucleotide
13
Other Nucleotides
 Nucleotides as enzyme assistants
 Coenzymes help enzymes promote and guide chemical
reactions
14
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
15
LE 5-26a
5 end
Nucleoside
Nitrogenous
base
Phosphate
group
Nucleotide
3 end
Polynucleotide, or
nucleic acid
Pentose
sugar
Nucleotide Polymers
 Two types:
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
17
DNA vs RNA
 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
18
Types of RNA
 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
 …. not exactly!
http://en.wikipedia.org/wiki/List_of_RNAs
19
DNA
Sugar–phosphate
backbone
LE 16-5
5 end
 Most celebrated
molecule of our time
 Hereditary
information
 Directs the
development of
biochemical,
anatomical,
physiological, and (to
some extent)
behavioral traits
Nitrogenous
bases
Thymine (T)
Adenine (A)
Cytosine (C)
Phosphate
Sugar (deoxyribose)
3 end
DNA nucleotide
Guanine (G)
Variation and Diversity
 Slight differences between
closely related individuals
 Distantly related individuals –
greater differences
© 2009 W.W. Norton & Company, Inc.
DISCOVER BIOLOGY 4/e
21
The Search for Genetic Material
 It needed to:
 Contain information
 Be easy to copy
 Be variable, to account for diversity
22
DNA or Protein?
 Nucleic Acids

First isolated 1869 -- Friedrich Miescher
 Proteins

Recognized in 18th C.

First described -- Gerardus Johannes Mulder

Named -- Jöns Jacob Berzelius in 1838.
23
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
24
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
25
Avery, MacLeod, & McCarty
1944
 Used the same assay system
 Isolated compounds from Strain S
 Added these to Strain R
 Only DNA transformed Strain R
26
Additional Evidence
 1947 -- Erwin Chargaff: DNA composition varies from
one species to the next

Makes DNA more credible
 By 1950s -- DNA composition known but not structure
LE 16-3
Hershey and Chase -- 1952
Phage
head
Tail
DNA
Bacterial cell
100 nm
Tail fiber
Hershey and Chase -- 1952
 DNA, not protein, is genetic material
29
LE 16-6
Rosalind Franklin
Franklin’s X-ray diffraction
photograph of DNA
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
31
LE 16-UN298
Purine + purine: too wide
Pyrimidine + pyrimidine: too narrow
Purine + pyrimidine: width
consistent with X-ray data
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
33
34
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
5 end
3 end
5 end
3 end
36
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
37
Replication
Models
 Meselson & Stahl
(1958)
Labeled strand -heavy isotope of
nitrogen
 Labeled free
nucleotides -lighter isotope of
nitrogen

Parent cell
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, complementary strand.
Dispersive model.
Each strand of
both daughter
molecules
contains
a mixture of
old and newly
synthesized
DNA.
First
replication
Second
replication
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)
First replication
Conservative
model
Semiconservative
model
Dispersive
model
Less
dense
More
dense
Second replication
DNA Replication: A Closer Look
 Quick and accurate
 More than a dozen enzymes and other proteins
participate
40
Replication
 Origins of Replication
 Eukaryotic chromosome -- hundreds to thousands
 Replication proceeds in both directions
 Replication fork – ends of each replication bubble
41
LE 16-12
Parental (template) strand
Origin of replication
Bubble
Daughter (new) strand
0.25 µm
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).
DNA Replication
 DNA Polymerase
 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
43
LE 16-13
New strand
5 end
Template strand
3 end
5 end
3 end
Sugar
Base
Phosphate
DNA polymerase
3 end
Pyrophosphate
Nucleoside
triphosphate
5 end
3 end
5 end
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

45
The DNA Replication Machine


Complex -probably
stationary
DNA
polymerase
 “reels in”
parental
DNA
 “extrude”
daughter
DNA
46