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chapter

DNA Metabolism 25
1. Conclusions from the Meselson-Stahl Experiment The Meselson-Stahl experiment (see Fig. 25–2)
proved that DNA undergoes semiconservative replication in E. coli. In the “dispersive” model of
DNA replication, the parent DNA strands are cleaved into pieces of random size, then joined with
pieces of newly replicated DNA to yield daughter duplexes. Explain how the results of Meselson and
Stahl’s experiment ruled out such a model.

Answer If random, dispersive replication takes place, the density of the first-generation DNA
in the Meselson-Stahl experiment would be the same as was actually observed: a single band
midway between heavy and light DNA. In the second generation, however, all the DNA would
again have the same density and would appear as a single band, midway between the band ob-
served in the first generation and that of light DNA; this was not observed. Two bands were
obtained in the experiment, ruling out the dispersive model.

2. Heavy Isotope Analysis of DNA Replication A culture of E. coli growing in a medium containing
15
NH4Cl is switched to a medium containing 14NH4Cl for three generations (an eightfold increase in
population). What is the molar ratio of hybrid DNA (15N–14N) to light DNA (14N–14N) at this point?

Answer This experiment is an extension of the Meselson-Stahl experiment, which demon-

strates that replication in E. coli is semiconservative. After three generations the molar ratio
of 15N–14N DNA to 14N–14N DNA is 2/6  0.33.

3. Replication of the E. coli Chromosome The E. coli chromosome contains 4,639,221 bp.
(a) How many turns of the double helix must be unwound during replication of the E. coli chromosome?
(b) From the data in this chapter, how long would it take to replicate the E. coli chromosome at 37 C
if two replication forks proceeded from the origin? Assume replication occurs at a rate of 1,000 bp/s.
Under some conditions E. coli cells can divide every 20 min. How might this be possible?
(c) In the replication of the E. coli chromosome, about how many Okazaki fragments would be
formed? What factors guarantee that the numerous Okazaki fragments are assembled in the
correct order in the new DNA?

Answer
(a) During DNA replication, the complementary strands must unwind completely to allow
the synthesis of a new strand on each template. Given the 10.5 bp/turn in B-DNA, and
approximating the E. coli chromosome as 4.64  106 bp,
number of base pairs
the number of helical turns  
number of base pairs per helical turn
4.64  106 bp
   4.42  105 turns
10.5 bp/turn

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S-284 Chapter 25 DNA Metabolism

(b) Chromosomal DNA replication in E. coli starts at a fixed origin and proceeds bidirection-
ally. Each replication fork travels (4.64  106 bp)/2  2.32  106 bp during replication.
If we assume a replication rate of 1,000 bp/s, the time required for the completion of
DNA synthesis in each replication fork is
(2.32  106 bp)/[(1000 bp/s)(60 s/min)]  40 min
This is about twice the time required for cell division. One possible explanation is
that replication of an E. coli chromosome starts from two origins, each proceeding bidi-
rectionally to yield four replication forks. In this mode, it would take 20 min to complete
the replication of the chromosome. However, we know there is only one replication ori-
gin in the E. coli chromosome.
An alternative explanation is that a new round of replication begins before the previ-
ous one is completed: for cells dividing every 20 min, a replicative cycle is initiated every
20 min, and each daughter cell receives a chromosome that is half-replicated. This latter
mode has been experimentally verified.
(c) The Okazaki fragments in E. coli are 1,000 to 2,000 nucleotides long, so (4.64  106
nucleotides)/(2000 nucleotides) to (4.64  106 nucleotides)/(1000 nucleotides)  2,000
to 5,000 Okazaki fragments are formed. The fragments are firmly bound to the template
strand by base pairing, and each fragment is quickly joined to the lagging strand by the
successive action of DNA polymerase I and DNA ligase, thus preserving the correct order
of the fragments. A mixed pool of Okazaki fragments, detached from their template, does
not form during normal replication.

4. Base Composition of DNAs Made from Single-Stranded Templates Predict the base composi-
tion of the total DNA synthesized by DNA polymerase on templates provided by an equimolar mixture
of the two complementary strands of bacteriophage fX174 DNA (a circular DNA molecule). The base
composition of one strand is A, 24.7%; G, 24.1%; C, 18.5%; and T, 32.7%. What assumption is neces-
sary to answer this problem?

Answer The sequence of a strand of duplex DNA is complementary to that of the other
strand, as determined by Watson-Crick base pairing (A with T, and G with C). The DNA strand
made from the given template strand has A, 32.7%; G, 18.5%; C, 24.1%; T, 24.7%. The DNA
strand made from this complementary template strand has A, 24.7%; G, 24.1%; C, 18.5%; T,
32.7%. Thus, the composition of the total DNA synthesized is calculated as, for A, (32.7% 
24.6%)/2  28.7%; similarly, G  21.3%; C  21.3%; T  28.7%. We are assuming that both
template strands are completely replicated.

5. DNA Replication Kornberg and his colleagues incubated soluble extracts of E. coli with a mixture of
dATP, dTTP, dGTP, and dCTP, all labeled with 32P in the a-phosphate group. After a time, the incuba-
tion mixture was treated with trichloroacetic acid, which precipitates the DNA but not the nucleotide
precursors. The precipitate was collected, and the extent of precursor incorporation into DNA was
determined from the amount of radioactivity present in the precipitate.
(a) If any one of the four nucleotide precursors were omitted from the incubation mixture, would ra-
dioactivity be found in the precipitate? Explain.
(b) Would 32P be incorporated into the DNA if only dTTP were labeled? Explain.
(c) Would radioactivity be found in the precipitate if 32P labeled the b or g phosphate rather than
the a phosphate of the deoxyribonucleotides? Explain.

Answer
(a) No. Incorporation of 32P into DNA results from the synthesis of new DNA, which re-
quires the presence of all four nucleotide precursors.
(b) Yes. Although all four nucleotide precursors must be present for DNA synthesis, only
one of them has to be radioactive in order for radioactivity to appear in the new DNA.
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Chapter 25 DNA Metabolism S-285

(c) No. No radioactivity would be incorporated if the 32P label were not at the a phosphate
because DNA polymerase, which catalyzes this reaction, cleaves off pyrophosphate—that
is, the b and g phosphate groups.

6. The Chemistry of DNA Replication All DNA polymerases synthesize new DNA strands in the
5n3 direction. In some respects, replication of the antiparallel strands of duplex DNA would be sim-
pler if there were also a second type of polymerase, one that synthesized DNA in the 3n5 direction.
The two types of polymerase could, in principle, coordinate DNA synthesis without the complicated
mechanics required for lagging strand replication. However, no such 3n5-synthesizing enzyme has
been found. Suggest two possible mechanisms for 3n5 DNA synthesis. Pyrophosphate should be one
product of both proposed reactions. Could one or both mechanisms be supported in a cell? Why or
why not? (Hint: You may suggest the use of DNA precursors not actually present in extant cells.)

Answer Mechanism 1: 3-OH of an incoming dNTP attacks the  phosphate of the triphos-
phate at the 5 end of the growing DNA strand, displacing pyrophosphate. This mechanism
uses normal dNTPs, and the growing end of the DNA always has a triphosphate on the 5 end.

5 end Z
P P P CH2 O

Z H H
H H
P P P CH2 O
O H
H H PPi
H H 
O P O
OH H O
Y
:

5 end Y CH2 O
P P P CH2 O
H H
H H H H
H H
O H
O H 
O P O

O P O
O X
O X CH2 O
CH2 O
H H
H H H H
H H
O H
O H 
O P O

O P O
O
...

O 3 end
...

3 end
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S-286 Chapter 25 DNA Metabolism

Mechanism 2: This uses a new type of precursor, nucleotide 3-triphosphates. The growing
end of the DNA strand has a 5-OH, which attacks the  phosphate of an incoming
deoxynucleotide 3-triphosphate, displacing pyrophosphate. Note that this mechanism would
require the evolution of new metabolic pathways to supply the needed deoxynucleotide
3-triphosphates.

5 end Z
HO CH2 O
Z
HO CH2 O H H
H H
H H PPi
H H O H

O P O
OH H
5 end O
P Y Y
:

HO CH2 O CH2 O
P
H H H H
H H H H
P
O H O H
 
O P O O P O
O X O X
CH2 O CH2 O
H H H H
H H H H

O H O H
 
O P O O P O
O O
...
...

3 end 3 end

7. Leading and Lagging Strands Prepare a table that lists the names and compares the functions of
the precursors, enzymes, and other proteins needed to make the leading strand versus the lagging
strand during DNA replication in E. coli.

Answer In DNA replication, the leading strand is produced by continuous replication of the
DNA template strand in the 5 → 3 direction. The lagging strand is synthesized in the form
of short Okazaki fragments, which are then spliced together. The following table lists the par-
ticipants in DNA replication in E. coli.
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Leading Lagging
Component Function strand strand
dNTPs (dATP, dGTP, dGTP, dTTP) Source of new nucleotides for new DNA strand; X X
ATP energy source
Template Parent strand provides information for identities X X
of incoming nucleotides; stabilizes association of
nucleotides in growing strand by base-pairing
reactions.
DNA primer Provides a free 3 OOH, the point of X
attachment for incoming nucleotides
DNA helicase Unwinds double-stranded DNA just ahead of the X X
replication fork; requires ATP
DNA gyrase Topoisomerase that favors unwinding of the DNA X X
at the replication fork by twisting the DNA;
requires ATP
Single-stranded DNA–binding proteins Prevents base pairing of unwound DNA strands; X X
stabilizes single-stranded DNA
DNA polymerase III Elongates the new DNA strand by adding X X
nucleotides; requires the cofactors
Mg2 and Zn2
Pyrophosphatase Hydrolyzes the PPi released by polymerase X X
activity; helps “pull” the reaction in the
forward direction.
RNA primer Same as DNA primer; used to start each X
Okazaki fragment
Primase Synthesizes RNA primer X
NTPs (ATP, GTP, CTP, UTP) Used in synthesis of RNA primer X
DNA polymerase I Exonuclease that removes RNA primer by
replacing NMPs with dNMPs in Okazaki X
fragments; requires the cofactors
Mg2 and Zn2
DNA ligase Joins the Okazaki fragments in the lagging strand X
by catalyzing the formation of a phosphodiester
bond; requires NAD as energy source

8. Function of DNA Ligase Some E. coli mutants contain defective DNA ligase. When these mutants
are exposed to 3H-labeled thymine and the DNA produced is sedimented on an alkaline sucrose den-
sity gradient, two radioactive bands appear. One corresponds to a high molecular weight fraction, the
other to a low molecular weight fraction. Explain.

Answer During replication of the DNA duplex, the leading strand is replicated continuously
and the lagging strand is replicated in short fragments (Okazaki fragments), which are then
spliced together by DNA ligase. Mutants with defective DNA ligase produce a DNA “duplex” in
which one of the strands remains fragmented. Consequently, when this duplex is denatured by
the alkaline conditions of the sucrose gradient, sedimentation results in one fraction contain-
ing the intact single strand (the high molecular weight band) and one fraction containing the
unspliced fragments (the low molecular weight band).
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S-288 Chapter 25 DNA Metabolism

9. Fidelity of Replication of DNA What factors promote the fidelity of replication during the
synthesis of the leading strand of DNA? Would you expect the lagging strand to be made with the
same fidelity? Give reasons for your answers.

Answer Fidelity of replication is ensured by Watson-Crick base pairing between the template
and leading strand, and proofreading and removal of wrongly inserted nucleotides by the
3-exonuclease activity of DNA polymerase III. The same fidelity would be expected in the
lagging strand—perhaps. The factors ensuring fidelity of replication are operative in
the leading and the lagging strands, but the greater number of distinct chemical operations
involved in making the lagging strand might provide a greater opportunity for errors to arise.

10. Importance of DNA Topoisomerases in DNA Replication DNA unwinding, such as that occur-
ring in replication, affects the superhelical density of DNA. In the absence of topoisomerases, the
DNA would become overwound ahead of a replication fork as the DNA is unwound behind it. A bacterial
replication fork will stall when the superhelical density (j) of the DNA ahead of the fork reaches
0.14 (see Chapter 24).
Bidirectional replication is initiated at the origin of a 6,000 bp plasmid in vitro, in the absence of
topoisomerases. The plasmid initially has a j of 0.06. How many base pairs will be unwound and
replicated by each replication fork before the forks stall? Assume that each fork travels at the same
rate and that each includes all components necessary for elongation except topoisomerase.

Answer About 1,200 bp are unwound, or about 600 in each direction. The DNA is initially
negatively supercoiled, with an Lk of about 537 and Lk0 of about 571 (see Chapter 24). Un-
winding 571  537  34 turns of DNA relaxes the DNA, and further unwinding adds positive
supercoils. Unwinding another 79 turns (or 113 in all) brings the superhelical density in the
remaining wound DNA to about 0.14—the stalling point. These 113 turns are equivalent to
113 turns  10.5 bp/turn  1,190 bp, or about 1,200 bp.

11. The Ames Test In a nutrient medium that lacks histidine, a thin layer of agar containing ~109 Salmo-
nella typhimurium histidine auxotrophs (mutant cells that require histidine to survive) produces
~13 colonies over a two-day incubation period at 37 C (see Fig. 25–21). How do these colonies arise
in the absence of histidine? The experiment is repeated in the presence of 0.4 mg of 2-aminoanthracene.
The number of colonies produced over two days exceeds 10,000. What does this indicate about 2-
aminoanthracene? What can you surmise about its carcinogenicity?

Answer Occasionally, some of the histidine-requiring mutants spontaneously undergo back-

mutation and regain their capacity to synthesize histidine, and thus can grow in a medium
lacking histidine. The observation that only 13 of about 109 bacteria produce colonies indi-
cates that the rate of back-mutation is quite low. The addition of 2-aminoanthracene increases
the rate of back-mutations more than 800-fold, indicating that 2-aminoanthracene is muta-
genic. Because about 90% of 300 known carcinogens are mutagenic, these observations sug-
gest that 2-aminoanthracene is likely to be carcinogenic.

12. DNA Repair Mechanisms Vertebrate and plant cells often methylate cytosine in DNA to form
5-methylcytosine (see Fig. 8–5a). In these same cells, a specialized repair system recognizes G–T
mismatches and repairs them to GqC base pairs. How might this repair system be advantageous to
the cell? (Explain in terms of the presence of 5-methylcytosine in the DNA.)

Answer This is very similar to Problem 6 of Chapter 8. Spontaneous deamination of

5-methylcytosine produces thymine, and thus a G–T mismatched pair. Such G–T pairs are
among the most common mismatches in the DNA of eukaryotes. The specialized repair system
restores the GqC pair.
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Chapter 25 DNA Metabolism S-289

13. DNA Repair in People with Xeroderma Pigmentosum The condition known as xeroderma pig-
mentosum (XP) arises from mutations in at least seven different human genes (see Box 25–1). The
deficiencies are generally in genes encoding enzymes involved in some part of the pathway for human
nucleotide-excision repair. The various types of XP are denoted A through G (XPA, XPB, etc.), with a
few additional variants lumped under the label XP-V.
Cultures of fibroblasts from healthy individuals and from patients with XPG are irradiated with ul-
traviolet light. The DNA is isolated and denatured, and the resulting single-stranded DNA is character-
ized by analytical ultracentrifugation.
(a) Samples from the normal fibroblasts show a significant reduction in the average molecular weight
of the single-stranded DNA after irradiation, but samples from the XPG fibroblasts show no such
reduction. Why might this be?
(b) If you assume that a nucleotide-excision repair system is operative in fibroblasts, which step
might be defective in the cells from the patients with XPG? Explain.

Answer
(a) Ultraviolet irradiation of skin fibroblast DNA results in formation of pyrimidine dimers.
In normal fibroblasts, the damaged DNA is repaired by excision of the pyrimidine dimer.
One step in this process is cleavage of the damaged strand by a special excinuclease.
Thus, the denatured single-stranded DNA isolated from normal cells after irradiation
contains the many fragments caused by the cleavage, and the average molecular weight
is lowered. These fragments of single-stranded DNA are absent from the XPG samples,
as indicated by the unchanged average molecular weight.
(b) The absence of fragments in the single-stranded DNA from XPG cells after irradiation
suggests that the special repair excinuclease is defective or missing.

14. Holliday Intermediates How does the formation of Holliday intermediates in homologous genetic
recombination differ from their formation in site-specific recombination?

Answer During homologous genetic recombination, a Holliday intermediate may be formed

almost anywhere within the two paired, homologous chromosomes. Once formed, the branch
point of the intermediate can move extensively by branch migration. In site-specific recombi-
nation, the Holliday intermediate is formed between two specific sites, and branch migration is
generally restricted by heterologous sequences on either side of the recombination sites.

15. A Connection between Replication and Site-Specific Recombination Most wild strains of
Saccharomyces cerevisiae have multiple copies of the circular plasmid 2 (named for its contour
length of about 2 m), which has 6,300 bp of DNA. For its replication the plasmid uses the host
replication system, under the same strict control as the host cell chromosomes, replicating only once
per cell cycle. Replication of the plasmid is bidirectional, with both replication forks initiating at a
single, well-defined origin. However, one replication cycle of a 2 plasmid can result in more than two
copies of the plasmid, allowing amplification of the plasmid copy number (number of plasmid copies
per cell) whenever plasmid segregation at cell division leaves one daughter cell with fewer than the
normal complement of plasmid copies. Amplification requires a site-specific recombination system
encoded by the plasmid, which serves to invert one part of the plasmid relative to the other. Explain
how a site-specific inversion event could result in amplification of the plasmid copy number. (Hint:
Consider the situation when replication forks have duplicated one recombination site but not the
other.)

Answer Once replication has proceeded from the origin to a point where one recombination
site has been replicated but the other has not, site-specific recombination not only inverts the
DNA between the recombination sites but also changes the direction of one replication fork
relative to the other. The forks will chase each other around the DNA circle, generating many
tandem copies of the plasmid. The multimeric circle can be resolved to monomers by addi-
tional site-specific recombination events.
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S-290 Chapter 25 DNA Metabolism

Origin Origin
1 1
initiation of recombination at
replication sites 1 and 2 (inversion)

2 2
Plasmid with Partially
recombination replicated
sites 1 and 2 plasmid

Origin Origin
continued
unidirectional
replication

Plasmid with Multimeric

reoriented plasmid
replication forks

Data Analysis Problem

16. Mutagenesis in Escherichia coli Many mutagenic compounds act by alkylating the bases in DNA.
The alkylating agent R7000 (7-methoxy-2-nitronaphtho[2,1-b]furan) is an extremely potent mutagen.

CH3
O

NO2
O
R7000

In vivo, R7000 is activated by the enzyme nitroreductase, and this more reactive form covalently at-
taches to DNA—primarily, but not exclusively, to GmC base pairs.
In a 1996 study, Quillardet, Touati, and Hofnung explored the mechanisms by which R7000 causes
mutations in E. coli. They compared the genotoxic activity of R7000 in two strains of E. coli: the wild-
type (uvr) and mutants lacking uvrA activity (uvr; see Table 25–6). They first measured rates of
mutagenesis. Rifampicin is an inhibitor of RNA polymerase (see Chapter 26). In its presence, cells will
not grow unless certain mutations occur in the gene encoding RNA polymerase; the appearance of
rifampicin-resistant colonies thus provides a useful measure of mutagenesis rates.
The effects of different concentrations of R7000 were determined, with the results shown in the
graph following.
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Chapter 25 DNA Metabolism S-291

Rifampicin-resistant mutants produced

1,000

uvr uvr

100

10

1
0 0.2 0.4 0.6 0.8 1
R7000 (␮g/mL)

(a) Why are some mutants produced even when no R7000 is present?
Quillardet and colleagues also measured the survival rate of bacteria treated with different
concentrations of R7000.

100
Survival (%)

uvr
10

uvr

1
0 0.2 0.4 0.6 0.8 1
R7000 (␮g/mL)

(b) Explain how treatment with R7000 is lethal to cells.

(c) Explain the differences in the mutagenesis curves and in the survival curves for the two types of
bacteria, uvr and uvr, as shown in the graphs.
The researchers then went on to measure the amount of R7000 covalently attached to the DNA
in uvr and uvr E. coli. They incubated bacteria with [3H]R7000 for 10 or 70 minutes, extracted the
DNA, and measured its 3H content in counts per minute (cpm) per g of DNA.

3
H in DNA (cpm/g)
Time (min) uvr uvr

10 76 159
70 69 228

(d) Explain why the amount of 3H drops over time in the uvr strain and rises over time in the uvr
strain.
Quillardet and colleagues then examined the particular DNA sequence changes caused by
R7000 in the uvr and uvr bacteria. For this, they used six different strains of E. coli, each with a
different point mutation in the lacZ gene, which encodes -galactosidase (this enzyme catalyzes the
same reaction as lactase; see Fig. 14–10). Cells with any of these mutations have a nonfunctional
-galactosidase and are unable to metabolize lactose (i.e., a Lac phenotype). Each type of point
mutation required a specific reverse mutation to restore lacZ gene function and Lac phenotype. By
plating cells on a medium containing lactose as the sole carbon source, it was possible to select for
these reverse-mutated, Lac cells. And by counting the number of Lac cells following mutagenesis
of a particular strain the researchers could measure the frequency of each type of mutation.
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S-292 Chapter 25 DNA Metabolism

First, they looked at the mutation spectrum in uvr cells. The following table shows the results
for the six strains, CC101 through CC106 (with the point mutation required to produce Lac cells in-
dicated in parentheses).

Number of Lac cells (average  SD)

CC101 CC102 CC103 CC104 CC105 CC106
(AUT (GmC (GmC (GmC (AUT (AUT
R7000 to to to to to to
(g/mL) CmG) AUT) CmG) TUA) TUA) GmC)

0 63 11  9 21 53 21 11

0.075 24  19 34  3 84 82  23 40  14 42
0.15 24  4 26  2 95 180  71 130  50 32

(e) Which types of mutation show significant increases above the background rate due to treatment
with R7000? Provide a plausible explanation for why some have higher frequencies than others.
(f) Can all of the mutations you listed in (e) be explained as resulting from covalent attachment of
R7000 to a GmC base pair? Explain your reasoning.
(g) Figure 25–28b shows how methylation of guanine residues can lead to a GmC to APT mutation. Using a
similar pathway, show how a G–R7000 adduct could lead to the GmC to APT or TPA mutations shown
above. Which base pairs with the GOR7000 adduct?
The results for the uvr bacteria are shown in the table below.

Number of Lac cells (average  SD)

CC101 CC102 CC103 CC104 CC105 CC106
(AUT (GmC (GmC (GmC (AUT (AUT
R7000 to to to to to to
(g/mL) CmG) AUT) CmG) TUA) TUA) GmC)

0 22 10  9 33 42 61 0.5  1

1 76 21  9 83 23  15 13  1 11
5 43 15  7 22  2 68  25 67  14 11

(h) Do these results show that all mutation types are repaired with equal fidelity? Provide a plausible expla-
nation for your answer.

Answer
(a) Even in the absence of an added mutagen, background mutations occur due to radiation,
cellular chemical reactions, and so forth.
(b) If the DNA is sufficiently damaged, a substantial fraction of gene products are nonfunc-
tional and the cell is nonviable.
(c) Cells with reduced DNA repair capability are more sensitive to mutagens. Because they
less readily repair lesions caused by R7000, uvr bacteria have an increased mutation
rate and increased chance of lethal effects.
(d) In the uvr strain, the excision-repair system removes DNA bases with attached
[3H]R7000, decreasing the 3H in these cells over time. In the uvr strain, the DNA is not
repaired and 3H level increases as [3H]R7000 continues to react with the DNA.
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Chapter 25 DNA Metabolism S-293

(e) All mutations listed in the table except APT to GmC show significant increases over
background. Each type of mutation results from a different type of interaction between
R7000 and DNA. Because different types of interactions are not equally likely (due to
differences in reactivity, steric constraints, etc.), the resulting mutations occur with dif-
ferent frequencies.
(f) No. Only those that start with a GmC base pair are explained by this model. Thus APT
to CmG and APT to TPA must be due to R7000 attaching to an A or a T.
(g) R7000-G pairs with A. First, R7000 adds to GmC to give R7000-GmC. (Compare this
with what happens with the CH3-G in Fig. 25–28b, p. 1000.) If this is not repaired, one
strand is replicated as R7000-GPA, which is repaired to TPA. The other strand is wild-
type. If the replication produces R7000-GPT, a similar pathway leads to an APT base
pair.
(h) No. Compare data in the two tables, and keep in mind that different mutations occur at
different frequencies.
APT to CmG: moderate in both strains; but better repair in the uvr strain
GmC to APT: moderate in both; no real difference
GmC to CmG: higher in uvr; certainly less repair!
GmC to TPA: high in both; no real difference
APT to TPA: high in both; no real difference
APT to GmC: low in both; no real difference
Certain adducts may be more readily recognized by the repair apparatus than others and
thus are repaired more rapidly and result in fewer mutations.

Reference
Quillardet, P., Touati, E., & Hofnung, M. (1996) Influence of the uvr-dependent nucleotide excision repair on DNA adducts forma-
tion and mutagenic spectrum of a potent genotoxic agent: 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000). Mutat. Res. 358, 113–122.