Chapter 18 - Gene Mutations & Repair

Question 1

List the 3 important/main points in DNA mutations and repair.

Answer 1

1. The type of mutation (transition, missense, etc.)
2. The consequences of that mutation (change in pheno, impact on replication, etc).
3. How the organism deals with the mutation (remove + replace v. direct repair).

Question 2

Mutations in somatic cells occur at a rate of about one per __ cells per cell cycle.

Humans have more than __ somatic mutations, but the majority have no observable __.

Answer 2

1M

100M; phenotype

Question 3

Somatic mutations that stimulate cell division and growth are the basis of nearly all __.

Answer 3

cancers.

Question 4

Two categories of mutations are __ (division via mitosis) and __ (division via meiosis).

Answer 4

somatic; germline

Question 5

List the 4 gene mutations associated with a phenotypic effect.

Answer 5

Missense; nonsense; silent; neutral

Question 6

This gene mutation changes the codon which changes the amino acid.

Answer 6

Missense (it missed the “correct answer”; got it wrong).

Question 7

This gene mutation is likely to be problematic IF it occurs too early in the reading frame.

Answer 7

Nonsense mutation

Question 8

This gene mutation changes the codon from an amino acid to a stop codon.

Answer 8

Nonsense mutation

Question 9

This gene mutation changes the codon to a synonymous codon.

Answer 9

Silent mutation.

Question 10

This gene mutation is similar to a missense mutation; however, the incorrect AA is chemically similar to the original AA.

Answer 10

Neutral mutation

Question 11

This gene mutation often has a discernible change on the phenotype, but the change/effect is minimal.

Answer 11

Neutral mutation

Question 12

Insertions and deletions occur more frequently than __ substitutions.
These mutations can create __ mutations if the insertion or deletion is in the __.

Answer 12

base

frameshift; ORF

Question 13

__-__ insertions and deletions can lead to the addition or loss of an AA, but the protein may remain functional because the insertion / deletion is occurs in __ of __.

Answer 13

In-frame; multiples of 3

Question 14

Fragile X Syndrome is caused by an __ __ __ in the number of copies of __ (normally 60 copies becomes 100s or 1000s).

Answer 14

expanding nucleotide repeat; CGG

Question 15

Fragile X syndrome causes?

Answer 15

mental retardation. It’s fragile because it breaks in the lab.

Question 16

Huntington’s is an example of an __ __ repeat. The increase changes the AA sequence of the protein causing it to become more and more __.

Answer 16

expanding nucleotide

toxic

Question 17

A loss-of-function mutation is usually __; the other allele usually picks up the slack. An exception would be if the allele was __.

Answer 17

recessive.

haploinsufficient

Question 18

A loss-of-function mutation that causes complete loss is called a __ mutation.

Answer 18

null

Question 19

A loss-of-function mutation can be due to a mutation in the __ regions required for what 3 functions?

Answer 19

regulatory

transcription, splicing, or translation.

Question 20

Gain-of-function mutations create an entirely new __, or they cause the __ to appear in the wrong tissue, or at the wrong time of __. These mutations are usually __ since the novel phenotype would not be visible otherwise.

Answer 20

trait; trait; development

dominant

Question 21

__ mutations are expressed only under specific conditions. An example are temperature sensitive mutations: the normal phenotype is seen at __ temperatures whereas the mutant phenotype is seen at __ temps.

Answer 21

Conditional

permissive; nonpermissive

Question 22

__ mutations are the only type of mutation that can be studied in a haploid organism with a mutation in a gene that is essential for viability.

Answer 22

Conditional

Question 23

__ mutations are almost always recessive due to the fact that the organism won’t live to reproductive age to pass it along. The exception is __ disease.

Answer 23

Lethal; Huntingtons

Question 24

A __ mutation alters the WT to another phenotype; a __ mutation alters the mutant back to the WT.

A __ mutation also alters the mutant back to the WT, BUT it involves a second mutation rather than a ‘correction’ (2 wrongs make a right).

Answer 24

forward; reverse

suppressor

Question 25

An __ suppressor mutation occurs on the same gene; an __ mutation is on two different genes.

Answer 25

intragenic; intergenic

Question 26

A mutation at gene Z causes a nonsense mutation leading to early termination and a nonfunctional protein. A mutation in gene L yields an isoaccepting tRNA whose anticodon recognizes the nonsense codon in gene Z. What kind of mutation is this?

Answer 26

Intergenic suppressor mutation: 2 wrongs made a right.

Question 27

Mutation __ describe how often a specific gene undergoes mutation (expressed as # of mutations per cell division or gamete).

Mutation __ describe the incidence of a specific mutation within a population of organisms.

Answer 27

rates

frequencies

Question 28

“Achondroplasia (form of dwarfism) is due to a mutation that occurs at a frequency of about 4 per 100K gametes.”

This is an example of a mutation __.

Answer 28

rate

Question 29

“1 in 20K individuals carries the mutation for achondroplasia (form of dwarfism).”

This is an example of a mutation __.

Answer 29

frequency

Question 30

Rare and very short-lived shifts in electrons that alter the base pairing potential are known as __ shifts.

This theory was proposed by Watson and Crick, but it is more likely that mispairing is a result of __.

Answer 30

Tautomeric

Wobble

Question 31

__-__ wobble and __-__ protonated wobble are most likely what cause nucleotide base mispairings.

But tautomeric shifts between __ (rare form) and __ (common form); or __ (rare form) and __ (common form) are possible, though unlikely.

Answer 31

Thymine-guanine
Cytosine-adenine

C(rare)-A
G(rare)-T
**CAG-T

Question 32

Strand __ often occurs at sites of __ DNA sequences.

If the new strand loops/slips out, the result will be an __ of a nucleotide on the __ strand. If the old strand loops/slips out, the result will be a __ of a nucleotide on the __ strand.

Answer 32

slippage; repetitive

addition; new
deletion; new

Question 33

Mammalian cells in culture loose about 10K __ per day by cleavage of the __ bond between the purine and the _‘C on the sugar.

Answer 33

purines; glycolytic; 1

Question 34

T or F: Deamination only occurs as a result of chemical exposure.

Answer 34

False; it can be spontaneous

Question 35

Deamination of cytosine creates __. Deamination of 5-methylcytosine (CpG islands) creates 5-methyl__, which is actually __.

Answer 35

uracil

5-methyluracil; thymine

Question 36

5-methylcytosine (5mC) is a __ for mutations for two reasons:

(1) deamination of 5mC creates __ which is actually __ - a legit DNA base - so it isn’t readily caught by the repair systems.
(2) __ will pair with A during the next replication causing : to : transition mutation.

Answer 36

hotspot
5mU; thymine
thymine
C:G to T:A

Question 37

5-bromouracil (5BU) has the same structure as thymine, but it has __ instead of a __ group at the 5 position of the base. This makes 5BU an __ of thymine.

The __ form of 5BU occasionally mispairs with __ leading to a T:A → C:G transition mutation.

Answer 37

Br; methyl;
analog;
ionized; guanine

Question 38

2-__ is an analog of adenine that occasionally mispairs with __; this mispairing causes a T:A → C:G __ mutation.

Answer 38

aminopurine; cytosine; transition

Question 39

Chemically induced mutations can be caused by base __; __ agents that add methyls and ethyls; __ (removal of the amine group); __ reactions from reactive oxygen species; and __ agents (planar molecules).

Answer 39

analogs; alkylating; deamination; oxidative, and intercalcalating

Question 40

Ethyl methanesulfonate (EMS) is an especially strong __ agent. It alters base pairing during __ and produces C:G to T:A AND T:A to C:G __ mutations.

Answer 40

alkylating;

replication; transition

Question 41

Ethyl methanesulfonate (EMS) causes C:G to T:A AND T:A to C:G transition mutations. What other type of mutations are each of these?

Answer 41

Forward and reverse

Question 42

__ __is a chemical mutagen that can deaminate bases.

Deamination of cytosine produces __ which pairs with adenine; deamination of __ produces xanthine which pairs with thymine. Both of these form C:G to T:A __ mutations.
Deamination of __ produces hypoxanthine with pairs with cytosine. This forms a T:A to C:G __ mutation.

Due to the C:G to T:A and T:A to C:G activity, __ __ can cause forward and reverse mutations.

Answer 42

Nitrous acid;
uracil; guanine;
transition;

adenine;
transition;

nitrous acid

Question 43

Reactive oxygen species (ROS) include __ anion, _ ₂ _ ₂, and __ radical.

Answer 43

superoxide; H₂O₂; hydroxyl

Question 44

__ agents are planar molecules about the size of a __. They cause changes to the __-__ structure of DNA and typically cause an insertion or deletion during replication (which leads to __ mutations).

Answer 44

Intercalcalating; nucleotide; aflotoxin.

3-D; frameshift

Question 45

__ radiation produces free radicals and reactive ions which cause __-__ breaks in DNA and lead to inversions, deletions, and ___.

Answer 45

Ionizing; double-stranded; translocations

Question 46

Nonionizing radiation includes __ light. It causes pyrimidine __ to form (pyrimidines that are __ bonded). • dimers are the most common and the most easily repaired, but C•C and C•T dimers are also possible.

Answer 46

UV.

dimers; covalently.

T•T

Question 47

UV light is an effective sterilizing agent because __ dimers distort the helix and block DNA __. The cell can survive if it can overcome the block, but this leads to increased __.

Answer 47

pyrimidine; replication.

mutagenisis

Question 48

The __ repair system allows replication to proceed past a pyrimidine __, but the mechanism is __. So while the cell survives, the price is increased __. The eukaryotic DNA poly used is DNA poly __; this poly functions by inserting - opposite dimers which is fine for the typical • dimer, but causes __ mutations for C•G dimers.

Answer 48

SOS; dimers; imprecise / error prone.

mutagenesis/mutations.

η; A-A; T•T; TRANSVERSION

Question 49

The SOS repair genes in E. coli are normally repressed by __. When replication is blocked by a pyrimidine dimer, a protein called __ binds to the ssDNA (at the __ fork) which, in turn, activates a protease. The protease degrades __ thereby inducing the SOS genes. The polymerase in this system is sloppy which earns the system being called an __-__ repair system.

Answer 49

LexA.

RecA; replication.

LexA.

error-prone

Question 50

Eukaryotes have a system similar to prokaryotic SOS that uses DNA poly __ (__). It replicates past pyrimidine dimers (caused by __ light) by inserting A-A opposite the dimer. This works well for the most common dimer - • - but for C•T dimers, this strategy leads to C-G (original) to A-T __ mutations. This earns it being called an __-__ polymerase.

Answer 50

η (eta).

UV;

T•T; TRANSVERSION (not transition - C going to A is a transversion!!!).

error-prone

Question 51

__ repair is a DNA repair mechanism that occurs post synthesis. The old strand is distinguished from the new strand by __.

In E. coli, __ __ (Dam) methylates the __ in GATC sequences; however, methylation is __ post synthesis so that there is a period where the __ repair system can distinguish between the two strands. During this period, the DNA is __ (half methylated).

Answer 51

Mismatch.

methylation.

DeoxyAdenosine Methylase; A; delayed; mismatch.

hemimethylated.

Question 52

__ are 3 enzymes involved in the mismatch repair system of E. coli. __ binds to the mismatched base, and it forms a complex with __ and __. They look for the closest GATC sequence, and __ nicks the strand that has an unmethylated GATC sequence. __ degrade the DNA, then polymerase and ligase repair.

Answer 52

MutSHL.

MutS; MutH; MutL.

MutH;.

exonucleases

Question 53

__ is a direct repair system that uses light energy to break covalent bonds in pyrimidine dimers (usually •) caused by __ light. In eukaryotes, the enzyme that does this is called __.

Answer 53

Photoreactivation; T•T; UV.

photolyase

Question 54

In base __ repair, a DNA __ (family of enzymes) cleaves the __ bond between a damaged base and the 1’ C of sugar to remove it. Then AP __ cuts the __ bond on either side of the lesion. Lastly, exonucleases, DNA polys, and ligase remove and replace the damaged area. DNA poly __ (prokaryotes) is likely used for its poly. activity and its _’ to _’ exonuclease activity (removes ahead of the new stuff).

Answer 54

excision; glycosylase; glycolytic.

endonuclease; phosphodiester.

1; 5’ - 3’

Question 55

__ glycosylase recognizes that this base doesn’t belong in DNA (formed via __ of cytosine), so it __ the base. Next, AP __ cuts the __ bonds surrounding the lesion, then DNA poly __ (in prokaryotes) uses its __ activity to remove, and its __ activity to replace, then ligase stitches it all up.

Answer 55

Uracil; deamination; excises.

endonuclease; phosphodiester; 1; exonuclease; polymerase

Question 56

In base excision repair, AP endonucleases cleave at very specific sites starting with the _’ C to the _’ C such that, when removed, the fragment will be _’ to _’; and the strands left behind will begin with a _’ OH and a _’ C on the other strand.

Answer 56

5’; 3’; 5’ to 3’;

3’ OH; 5’

Question 57

__ excision repair is likely the most important DNA repair pathway for eukaryotes and prokaryotes. It involves an enzyme complex that scans DNA looking for lesions like pyrimidine __ or __ products.

Answer 57

Nucleotide.

dimers; alkylation

Question 58

Nucleotide excision repair:
The enzyme complex __ the area of DNA surrounding a lesion, then binds. __s stabilize the ssDNA. __ bonds are cleaved off center at each end, with ~ 20 nt remaining __ of the 5’ cut, and ~ 5 / 8 nt (euk/prok) remaining __ of the 3’ cut. The fragment dissociates, and DNA poly and ligase fix/stitch.

Answer 58

scans.

SSBs.

Phosphodiester; downstream; upstream.

Question 59

Xeroderma pigmentosum is a defect in the __ __ repair system.
Hereditary nonpolyposis colon cancer arises from mutations in the __ repair system.

Answer 59

; nucleotide excision.

mismatch

Question 60

Transposons are __: they’ve been found in every organism. They’re abundant in humans making about __% of the genome (although most in humans are __).

The most common in humans is the __ sequence (they’re repeated > __ times).

Answer 60

ubiquitous.
50%; inactive.

Alu; 1M

Question 61

When can transposons be mutagenic? List 2 ways.

Answer 61

(1) If they insert into a critical part of a gene (promoter, ORF, etc.).
(2) Thy can promote rearrangements (insertions, deletions, inversions, and translocations).

Question 62

The staggered cuts made pre-insertion of a transposon are made by __. This enzyme recognizes the __ repeats of the transposon.

The __ repeats will differ from copy to copy because they result from __ the gaps of DNA made by the staggered cuts.

Answer 62

transposase.
inverted.

direct; filling

Question 63

Transposons can be ___ (copy number increases with time) or they can be __ (copy number remains constant, but the flanking __ repeats will change with each subsequent jump).

Answer 63

replicative; nonreplicative; direct

Question 64

__ cause > 50% of Drosophila mutations. The Bar mutation is due to a __ caused by recombination between two __.

Answer 64

transposons.

duplication; transposons

Question 65

Which of the following types of gene mutations in a protein-coding gene usually have the least severe (i.e., deleterious) phenotype?
A. base deletions
B. nonsense substitutions
C. missense substitutions
D. expansion of a trinucleotide repeat
E. All of the above generate equally severe phenotypes.

Answer 65

C. missense substitutions

Question 66

A mutation in gene X overrides the effect of a previous mutation in gene Y and restores wild-type phenotype. The mutation in gene X is called a(n) ________

Answer 66

intergenic suppressor mutation.

Question 67

Mutations produced by a newly developed chemical can be reversed by an intercalating agent, but not by any known base analog. What type of mutations are likely caused by this chemical?

Answer 67

Frameshift mutation

Question 68

Which proteins are associated with the SOS repair system in E. coli? What do each do?

Answer 68

LexA and RecA

LexA is a repressor. RecA ‘wrecks’ LexA (indirectly) by binding to ssDNA (at the fork) and activating proteases that attack LexA.

Question 69

What would you expect to occur following UV irradiation of an E.coli strain with a mutation of the LexA gene such that the LexA protein could not be cleaved by RecA?

Answer 69

The cell would die due to unrepaired DNA since the SOS repair genes could not be expressed due to LexA being bound to promoters and repressing the gene.

Question 70

What is the function of DNA glycosylases?
A. Recognize and cleave phosphodiester bonds in DNA.
B. Recognize and remove modified bases from the sugar component of DNA
C. Reattach the two parts of DNA that result from double-strand breaks
D. Remove pyrimidine dimers from DNA of E. coli that result from exposure to UV light
E. Prevent strand slippage during DNA replication

Answer 70

B. Recognize and remove modified bases from the sugar component of DNA

Question 71

Which of the following is true about transposable elements?
A. They can promote DNA rearrangements.
B. They often generate short flanking direct repeats of the genome DNA where the transposon inserts.
C. Many possess short terminal inverted repeats.
D. They are found in the genomes of all organisms that have been examined.
E. All of the above are true.

Answer 71

E. All of the above are true.

Question 72

Which of the following is TRUE concerning somatic mutations?
A. They are only point mutations.
B. They can be passed on to offspring.
C. They only occur very early in development.
D. They are not genetically inherited by the progeny.
E. More than one of the choices A-D are correct

Answer 72

D. They are not genetically inherited by the progeny.

Question 73

A __ mutation is only expressed under specific experimental conditions.

Answer 73

Conditional

Question 74

A test for mutagens and potential carcinogens that is based on an increased reversion frequency in histidine auxotrophs (His-) of Salmonella is called the
A. Amber test
B. Mutagen Reversion test 
C. Ames test
D. Salmonella reversion test 
E. Auxotrophic reversion test

Answer 74

C. Ames test

Question 75

Which of the following mutations would probably cause constitutive (continuous) expression of the SOS repair system?
A. A LexA protein that is resistant to cleavage by the protease activity of RecA.
B. A LexA protein that does not bind to the “SOS Box” DNA.
C. A RecA protein that was unable to activate its associated protease activity.
D. A RecA protein that no longer bound to single-stranded DNA.
E. More than one of the above.

Answer 75

B. A LexA protein that does not bind to the “SOS Box” DNA.

Question 76

Most transposable elements are flanked by short direct repeats. How are these direct repeats formed?
A. The direct repeats result from repairing the staggered cuts created by the transposase as part of the mechanism of inserting the transposable element.
B. The direct repeats are the termini of the transposable element.
C. The direct repeats form during genetic recombination that is required for insertion of the transposable element into a DNA molecule such as a chromosome.
D. Direct repeats only occur if the transposable element inserts itself into the DNA at a replication fork during DNA synthesis.
E. Direct repeats only occur when the transposable element inserts itself into genomic DNA containing repetitive DNA.

Answer 76

A. The direct repeats result from repairing the staggered cuts created by the transposase as part of the mechanism of inserting the transposable element.vc

Question 77

The inherited autosomal recessive human disease called xeroderma pigmentosum results from a defect in the
A. Mismatch repair system
B. Photoreactivation system.
C. Uracil DNA glycosylase system.
D. Nucleotide excision repair system.
E. Select this answer if none of the choices A-D are correct

Answer 77

D. Nucleotide excision repair system.

Question 78

Binding of LexA to the promoter of the SOS genes represses transcription. Degradation of LexA by RecA leads to transcription. What type of regulation is this?
A. Neg Repressible
B. Neg Inducible
C. Pos Repressible
D. Pos Inducible.

Answer 78

B. Neg Inducible

Neg is obvious. Inducible because RecA induces.

Question 79

Nucleotide excision v. base excision repair mechanisms?

Answer 79

Nucleotide excision uses and enzyme complex that unwinds DNA, then excises the bad stuff.

Base excision repair uses glycosylases to create an apurinic site, then DNA poly 1 uses its 5’-3’ exonuclease and 5’-3’ endonuclease activity to repair.