Download AP Biology Unit 4 Continued

AP Biology
Chapter 9
Griffith 1928
• Proved transformation of bacteria into a
mouse
• Had two strains of bacteria
– An avirulent or nonlethal strain (R)
– A virulent of lethal strain (S)
Griffith’s Experiment
• When he put the virulent strain in the mouse, it
died
• When he put the avirulent strain in the mouse,
the mouse lived!
• Then he heated the virulent strain and then put it
into the mouse and the mouse lived!
• When he put the heated virulent strain + the
nonvirulent strain into the mouse, the mouse
died 
• Why?
Explanation
• Transformation had occurred
• The nonvirulent bacteria took up
something in the dead heated virulent
strain: a “transforming principle” and
changed the nonvirulent strain into a
virulent strain!!
Other Scientists of interest
• Before 1940, biologists thought that
proteins were the information molecules
because they were so complex and had a
lot of variety
• Avery, Macleod and McCarty in 1944
proved that the transformation principle in
Griffith’s experiment was DNA!
Other Scientists of interest
• Hershey and Chase in 1952 proved that
bacteriophages (viruses that attack
bacteria) inject DNA into bacterial cells
• Franklin and Wilkins used x ray diffraction
on DNA to determine the distances
between molecules
• Watson and Crick in 1953 came up with
the model of DNA
Chargaff’s rules
• He found a simple relationship in DNA
called the base pairing rules
– Adenine = Thymine
– Guanine = Cytosine
Watson and Crick
• Crick: English phage geneticist at the Cavendish
labs at Cambridge University, London England
• Watson: American postdoc in Crick’s lab
• Both visited Wilkins & Franklin routinely 1951-53
• Derived the overall concept of the chemical
relationship
• Considered how Chargaff’s rules represented the
structure of DNA
• Franklin’s X ray data
• Built little tin models of the nucleotides and put the
DNA model together like a TinkerToy set
• Correctly deduced the structure of DNA (double
helix)
The Double Helix
• This is the Watson
and Crick model
worked out in 1953
and published in a
single-page article in
Nature of that year.
• Was convincing
structurally: gave
evidence for how
DNA replicated
• Most famous biology
paper ever written!
DNA Structure
•
•
Called deoxyribonucleic acid
Made up of nucleotides which have 3
parts
1. sugar – deoxyribose
2. Phosphate
3. Nitrogen base
Deoxyribose
• Pentose sugar = 5 carbons
• Carbons on the sugar are numbered 1
through 5 and the first carbon (1’) is linked
to one of the four nitrogen bases (ACTG)
phosphate
• Is attached to the
5’ and 3’ carbon,
making a
phosphodiester
linkage
• Forms the sugar
phospate
backbone of DNA
(or the ladder)
Nitrogen base
• Remember these are connected to the 1’ carbon
of the sugar
• 2 groups
– Purines
• Have two ring structures
• Adenine and guanine
– Pyrimidines
• Have one ring structure
• Thymine and cytosine
• The number of purines = number of pyrimidines
DNA molecule
• Consists of 2 polynucleotide chains
arranged in a coiled double helix
• Helix is like a ladder
• Two strands run in opposite directions and
are said to be antiparallel to each other
– The nitrogen bases are bonded by hydrogen
bonds
– A = T and C=G according to Chargaff’s rules
Hydrogen bonds
What is the complement of
3’AGCTAC5’?
How Does DNA Replicate?
• Several research groups worked on this.
We’ll discuss one
• 1957: Matthew Meselsohn and Fred Stahl
• They had 3 hypotheses
1. DNA replication is “semiconservative”
– One old strand kept with each of the new molecules;
one old paired with one new strand
2. DNA replication is “conservative”
–
Double strand maintained intact; new strands are
together in the new molecule
3. DNA replication is “dispersive”
–
Strands cut up and the old and new DNA interspersed
in both new strands
Semiconservative
is correct!
• Each strand
acts as a
template for
the other,
and so the
mutation will
propagate
through
successive
generations.
How Does Replication Start?
• The replication complex binds at the origin of
replication, which is identified by a particular
base sequence. This is initiated by RNA primer
• Helicase unwinds the DNA, which is held open
with helix-destabilizing proteins. Replication
starts in the Y-shaped replication fork.
Replication Proceeds on Two Strands
• Nucleotides are always added to the 3’ end by DNA
polymerase, thus moving in the 3’ to 5’ direction
• but the new strands elongate in opposite directions
• The leading strand elongates into the fork
• The lagging strand elongates away from the fork
• Elongation proceeds smoothly on the leading strand
Leading and Lagging Strands
• As the fork grows, both new strands elongate
further
• Subunit addition to the lagging strand is by 1002000 base Okazaki fragments.
• The lagging strand grows in a discontinuous
manner because of the size of the Okazaki
fragments
• That’s why it lags
The Lagging Strand
• Notice that the lagging strand is always
growing away from the replication fork
• The gaps between the Okazaki
fragments are joined together by DNA
ligase
In Action!
Review of Enzymes
•
•
•
•
•
Unwinds the DNA
Puts down RNA primer
Adds bases to strands
Seals Okazaki fragments up
Winds the DNA molecule back together
DNA Repair
• DNA polymerase proofreads what bases
had been laid down
• If there is a mistake, it will go back and
remove the wrong base and fix it
How does DNA fit in the cell?
• By histones
– Positively charged proteins (due to the high
number of amino acids)
– Are able to associate with DNA which is
negatively charged (due to the phosphate
groups)
• Histones and DNA form structure called
nucleosome
Nucleosome
• Are 8 histones with
DNA wrapped
around it
• Are part of the
chromatin
• Prevent DNA
strands from
becoming tangled
Cellular Ageing and DNA
• The replication process never entirely
completes at the ends of the
chromosomes
• However, DNA is protected at its ends
with long strands that do not carry any
genetic information, called telomeres
• as we age, they become shorter
• They are repaired and lengthened with
an enzyme called telomerase
• Loss of telomerase activity may be an
important cause of cellular aging