Download DNA Structure and Function

DNA Structure and
Function
Nucleic Acids (polymer)
• Monomer = nucleotides, the
building blocks of nucleic acids
• Structure = three parts: sugar,
phosphate, and nitrogencontaining base
Sugar-Phosphate Backbone
• Nucleotides
connected together
with a covalent
bond.
• Alternating sugars
and phosphates
Nucleic Acids
• DNA: Four bases:
o
o
o
o
Adenine (A)
Guanine (G)
Thymine (T)
Cytosine (C)
• Sugar is deoxyribose
• Double stranded
• RNA: Four bases:
o
o
o
o
Adenine (A)
Guanine (G)
Uracil (U, replaces T)
Cytosine (C)
• Sugar is ribose
• Single stranded
Nitrogenous Bases
• DNA -Four bases:
o
o
o
o
Adenine (A)
Guanine (G)
Thymine (T)
Cytosine (C)
• Memory trick,
pyrimidines have a
“y” in the name
Base Pairing
• DNA is 2 strands
(molecules) held
together by H-bonds
• Bases form hydrogen
bonds with each other
– A pairs with T (& vc vs)
– C pairs with G (& vc vs)
DNA
Where are
the H-bonds?
DNA Structure
• The bonds between
which 2 bases are
stronger G&C or A&T?
• H-bonds are very
week, break & reform
• W/ thousands of bases
& thousands of bonds,
DNA is held together
DNA
• DNA is a polar molecule
• It also has a negative charge
Griffith’s Experiment
• 1928
• Two strains of bacteria
– R – harmless (1)
– S – deadly (2)
• Heat killed Strain S is
also harmless (3)
• Something from heat
killed Strain S makes
Strain R deadly (4)
Avery, MacLeod, and McCarty
•
•
•
•
•
1944
Isolated compounds from Strain S
Added these to Strain R
DNA transformed Strain R into Strain S
“Proved” DNA was the genetic material
Determining that DNA is the
Genetic Material
Head
DNA
Tail
Tail fiber
300,000
• HERSHEY –
CHASE: 1952
• Determined that
the heredity
material was DNA
& not protein
• Studied the
bacteria virus T2
Determining that DNA is the
Genetic Material
Phage
Bacterium
Radioactive
protein
DNA
Batch 1
Radioactive
protein
Mix radioactively
labeled phages with
bacteria. The phages
infect the bacterial cells.
Batch 2
Radioactive
DNA
Empty
protein shell
Phage
DNA
Radioactivity
in liquid
Centrifuge
Agitate in a blender to
separate phages outside
the bacteria from the
cells and their contents.
Pellet
Centrifuge the mixture
Measure the
so bacteria form a
radioactivity in
pellet at the bottom of
the pellet and
the test tube.
the liquid.
Radioactive
DNA
Centrifuge
Pellet
Radioactivity
in pellet
The Structure of DNA
• FRANKLIN and
WILKINS: 1950’s
• X-ray crystalography
determined that DNA
is a double helix
The Structure of DNA
• WATSON and
CRICK: 1953
• Determined that DNA
was a double helix
• Made a DNA model
Determining the Structure of
DNA
• http://www.pbs.org/wgbh/nova/photo51/
DNA Structure in more detail
Two strands run in
opposite directions
Nucleotide Functions
Nucleotides Play Diverse Roles in
Organisms:
1. Used as “energy currency” in cells (ATP)
2. Are chemical messengers of cells, (cAMP)
3. Nucleotide coenzymes transport electrons
and hydrogen atoms (examples: NADH and
FADH2)
4. Nucleotides also serve as building blocks for
nucleic acids
Nucleic Acid Functions
1. DNA stores genetic information (traits and
inheritance)
2. RNA translates this genetic info into
protein
Organization of DNA
• Prokaryotes
– Several million base pairs one circular piece
– Related genes grouped
together
– Mostly coding DNA
– Nucleus?
20
Organization of DNA
• Eukaryotes
– Billions of base pairs –
several linear
chromosomes
– Genes not grouped
– Mostly non-coding
DNA
– Nucleus?
21
DNA in the cell
• Humans have 3 billion
nucleotide base pairs
• Roughly 6 feet of
DNA in the nucleus of
each cell
• How does it all fit?
DNA Packaging
• Eukaryotic chromosomes are very large
• Must be packaged
– Unavailable for transcription
• Unpacking must occur before transcription
Levels of DNA
Packaging
• Fully condensed,
seen at metaphase
• Tightly packed loops
• 30 nm fibers
• Histone spool
• Double helix
Chromosome Animation
• http://www.biostudio.com/demo_freeman_
dna_coiling.htm
Gene Expression
• Every cell in your body came
from 1 original egg and sperm
• Every cell has the same DNA
and the same genes
• Except the gametes which
have half the DNA/genes
26
Gene Expression
• Every cell has the same DNA, yet,
each cell is different, specialized
• Differences due to gene
expression
– Which genes are turned on/off
– How much product they make
27
Gene Expression
• DNA must be copied
when cells divide so
that DNA is the same
in all cells
DNA Replication
• DNA Synthesis during Sphase of Interphase (will
discuss w/ mitosis)
• H-bonds between 2
strands are broken
• Two Strands separate
• Each strand is a template
for the other
DNA Replication
• The Watson-Crick model of DNA
replication:
A
T
A
T
C
G
C
G
G
C
G
A
T
A
T
A
T
Parental
molecule
of DNA
A
C
C
Nucleotides
Both parental
strands serve
as templates
T
A
T
A
T
G
C
G
C
G
C
G
C
G
C
T
A
T
A
T
A
T
A
T
A
Two identical
daughter molecules
of DNA
DNA Replication
• http://www.fed.cuhk.e
du.hk/~johnson/teachi
ng/genetics/animation
s/dna_replication.htm
• DNA replication
review
DNA Replication
• Helicase breaks hydrogen bonds to
separate strands
• DNA Polymerase pairs new bases and
creates two new strands Semiconservative
• DNA segments connected by ligase
When does the cell replicate DNA?
• Before cell division so that new cells have
enough DNA to divide
• Cells divide in embryogenesis, wound repair, cell
replacement
DNA Structure Review
• Covalent bonds hold
a strand together
• Hydrogen bonds hold
two strands together
– A pairs with T
– C pairs with G
• Each strand is used
as a template to
replicate DNA
DNA Replication
• If the DNA is not replicated correctly,
mistakes occur.
• Polymerase and other enzymes can
correct mistakes.
• If they are not corrected, they result in
mutation, a permanent change in DNA.
Two Types of Mutations
• Base Changes
– A change in the sequence of nucleotide bases
– Most are silent (do not change a protein)
• Chromosomal Abnormalities (macromutations)
– Large changes in whole regions of DNA
– Most are lethal
Base Mutations
• Incorrect base-pairings that are not fixed
– Mutagens increase the frequency
• Next replication includes these changes
• Source of new alleles (new variation)
– A few are beneficial (make a better protein)
– Most are silent (make no change in a protein)
– Some are harmful (most that change a
protein)
Mutations
• Ask for examples of mutant human genes
• Bad mutations include ->
– sickle cell anemia, hemophilia, color
blindness.
• Can you find a mutation in this picture?
Can you find two mutations?
(There are at least two.)
Mutations:
• blue eyes & white skin
(occurred long ago).
• some say …
DNA Repair
• DNA polymerases often
insert incorrect bases
– DNA mismatch
• Proofreading enzymes
correct mistakes
DNA Repair
• Enzymes recognize
damaged DNA
• Cut the backbone on
either side
• Damaged DNA is
removed
• DNA is corrected