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Chapter 16: The Molecular Basis of Inheritance
Points of Emphasis
Know:
1. all the bold-faced terms
2. Know the researchers and what experiments they did and
what their experiments demonstrated (proved/revealed)
3. Know the process of DNA replication including all the
enzymes.
4. Be sure to understand the difference between the terms,
leading and lagging strand.
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Figure 16.0 Watson and Crick
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Figure 16.1 Transformation of bacteria
Griffith’s work with transforming bacteria
His work showed that “molecules” from the dead cells had converted or transformed
the R or nonpathogenic bacteria into S (pathogenic) bacteria
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Figure 16.2a The Hershey-Chase experiment: phages
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Figure 16.2ax Phages
Cell infected by phages
(viruses that infect
bacteria)
H & C labeled one group
of phage’s proteins with
radioactive S, another
group with radioactive P
of their DNA.
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Figure 16.2b The Hershey-Chase experiment
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Figure 16.3 The structure of a DNA stand
Chargaff: it was already known of what
DNA was composed and when Chargaff
analyzed DNA for its base composition he
found that no matter what organism the
%A’s = %T’s and %C’s = %G’s. These
percentages were different in different
organisms however.
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Figure 16.4 Rosalind Franklin and her X-ray diffraction photo of DNA
It was the pattern that RF discovered that indicated to Watson that DNA was helical
and some of its dimensions, indicating that DNA was a double helix.
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Figure 16.5 The double helix
The uniform diameter of RF’s X-ray indicated to Watson that A did not bind with A
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because they both were 2-ringed structures and C and T were 3-ringed so the diameter
would not be uniform.
Unnumbered Figure (page 292) Purine and pyridimine
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Figure 16.6 Base pairing in DNA
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Figure 16.7 A model for DNA replication: the basic concept (Layer 1)
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Figure 16.7 A model for DNA replication: the basic concept (Layer 2)
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Figure 16.7 A model for DNA replication: the basic concept (Layer 3)
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Figure 16.7 A model for DNA replication: the basic concept (Layer 4)
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Figure 16.8 Three alternative models of DNA replication
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Figure 16.9 The Meselson-Stahl experiment tested three models of DNA replication
(Layer 4)
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Figure 16.10 Origins of replication in eukaryotes
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Figure 16.11 Incorporation of a nucleotide into a DNA strand
DNA Polymerase
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Figure 16.12 The two strands of DNA are antiparallel
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Figure 16.13 Synthesis of leading and lagging strands during DNA replication
The addition of the new nucleotides
starts with the construction or presence
of an RNA primer. This RNA primer is
made by primase.
DNA polymerase later removes the
RNA primer and replaces it with
nucleotides.
Topoisomerase
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Figure 16.14 Priming DNA synthesis with RNA
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Figure 16.15 The main proteins of DNA replication and their functions
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Figure 16.16 A summary of DNA replication
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Figure 16.17 Nucleotide excision repair of DNA damage
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Figure 16.18 The end-replication problem
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Figure 16.19a Telomeres and telomerase: Telomeres of mouse chromosomes
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Figure 16.19b Telomeres and telomerase
Telomerase has some RNA along
with its enzyme action; this
serves as a template
Telomerase is not present in
most cells and the ends of our
somatic cell’s chromosomes do
shorten.
In gametes, telomerase
produces long telomeres.
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Quick Comments About DNA Replication
1. DNA polymerase will only add bases to a template strand,
therefore the template strand controls which of the four
deoxyribonucleotides (A, C, G or T) will be added.
2. The addition of the new bases is due to a large favorable free
energy change caused by the release of pyrophosphate and
its hydrolysis to two free inorganic phosphate groups.
3. At the replication fork, DNA of both new daughter strands is
synthesized by a multienzyme complex that contains the DNA
polymerase.
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4. No 3’ – 5’ DNA polymerase has ever been found.
5. The Okazaki fragments are 1000 – 2000 nucleotides long in
bacteria and 100 –200 nucleotides in length in eukaryotes.
6. The synthesis of the leading strand slightly proceeds the
lagging strand.
7. The synthesis of the lagging strand is delayed because it
must wait for the leading strand to expose the template strand
on which each Okazaki fragment is synthesized.
8. 1 mistake is made for every 1 billion nucleotides copied.
9. It is possible for a mismatch to occur where A bonds to C
instead of G without affecting the helix geometry.
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10. In the first step of proofreading by DNA polymerase, the
moving DNA polymerase has a higher affinity for the correct
nucleotide than an incorrect one because only the correct one
can base pair with the template.
11. After nucleotide binding, but before the nucleotide is
covalently bonded to the chain, the enzyme undergoes a
conformational change and incorrectly bound nucleotide is
more likely to dissociate during this step than a correct one.
12. When an incorrect nucleotide is located, a different part of the
DNA polymerase will clip it off.
13. An RNA primer is preferred to a DNA primer because the DNA
polymerase makes an error about 1 x 105. (There are other
processes where errors can occur totaling the earlier
mentioned 1 out of 1 billion). This would allow for errors in
about 5% of the total genome and this mutation rate would be
enormous.
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14. There really are two DNA helicases, one working on the
leading strand and one on the lagging strand.
15. DNA polymerase will synthesize only a short string of
nucleotides before falling off of the DNA. This allows quick
recycling for synthesizing the Okazaki fragments.
16. This rapid falling off is not productive on the leading strand
and there is a molecular “clamp” that keeps the polymerase
firming on the DNA when it is moving but releases as soon as
the polymerase encounters a double-stranded region of DNA
ahead.
17. On the leading strand, the moving DNA polymerase is tightly
bound to the clamp; on the lagging strand, each time the
polymerase reaches a 5’end of the preceding Okazaki
fragment, the polymerase is released.
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18. There is also a strand-directed mismatch repair system. This
detects distortions in the DNA helix due to the misfit between
noncomplementary bases. This makes errors about 1 out of
100 times. This system can identify the mismatch on the
newly synthesized strand. In bacteria, the parent strand is
methylated and the new bases or unmethylated and can be
recognized. In eukaryotic cells, newly synthesized strands
are nicked or have single-stranded breaks that is a signal for
the proofreading system.
19. A mismatch repair gene can be defective and has been
associated with a type of colon cancer, hereditary
nonpolyposis colon cancer.
20. There really are two topoisomerases; one nicks one of the two
DNA strands, another cuts both strands.
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21. Prokaryotes have a single origin of replication. Their circular
piece of DNA is much smaller than eukaryotes (E. coli is 4.6 x
106 base pairs); replicates at about 500 – 1000 nucleotides per
second.
22. Eukaryotic chromosomes are much larger; new bases are
added on at a rate of about 50 nucleotides per second and
with an average human chromosome containing about 150
million nucleotide pairs, it would take about 800 hours if a
different strategy did not evolve. Hence the presence of
multiple replication forks.
23. In eukaryotes, replication origins are activated in clusters
called replication units (20-80 origins). Within a unit the
individual origins are spaced at intervals of 30,000 to 300,000
nucleotide pairs from one another.
24. That’s enough isn’t it?????
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