Deck 7: DNA Repair Pathways

Question 1

An induced mutation occurs

A) as a result of natural processes in cells.
B) as a result of interaction of DNA with an outside agent.
C) spontaneously.
D) as a result of DNA replication errors.

Answer 1

as a result of interaction of DNA with an outside agent.

Question 2

A transition mutation is one in which

A) one pyrimidine base is replaced with another, or one purine base with another.
B) one pyrimidine base is replaced with a purine base or vice versa.
C) there is an A to T substitution.
D) there is a C to G substitution.

Answer 2

one pyrimidine base is replaced with another, or one purine base with another.

Question 3

A transversion mutation is one in which

A) one pyrimidine base is replaced with another, or one purine base with another.
B) one pyrimidine base is replaced with a purine base or vice versa.
C) there is a C to T substitution.
D) there is an A to G substitution.

Answer 3

one pyrimidine base is replaced with another, or one purine base with another.

Question 4

A nonsense mutation is one in which:

A) the altered codon codes for the same amino acid.
B) the altered codon codes for a different amino acid.
C) the mutant protein is shorter than normal.
D) insertion or deletion results in a shift in the reading frame.

Question 5

A silent mutation is one in which

A) the altered codon codes for the same amino acid.
B) the altered codon codes for a different amino acid.
C) the mutant protein is shorter than normal.
D) insertion or deletion results in a shift in the reading frame.

Question 6

A missense mutation is one in which

A) the altered codon codes for the same amino acid.
B) the altered codon codes for a different amino acid.
C) the mutant protein is shorter than normal.
D) insertion or deletion results in a shift in the reading frame.

Question 7

A type of mutation that results in multiple adjacent amino acid changes in a polypeptide is probably caused by the following type of mutation:

A) frameshift
B) transversion
C) transition
D) missense

Question 8

Which mutagen does not covalently modify DNA?

A) UV light
B) base analogs
C) intercalating agents
D) ionizing radiation

Question 9

Which statement is not true about the deamination of cytosine?

A) Deamination can occur spontaneously from the action of water
B) Deamination is an example of DNA damage resulting in a single base change.
C) Methylated cytosine is protected from deamination.
D) Deamination converts cytosine to uracil.

Question 10

The most frequent ultraviolet (UV) light-induced lesions of DNA are

A) oxidation of guanine to generate 8-oxoguanine.
B) formation of a cyclobutane ring between adjacent thymines, forming a thymine dimer.
C) induction of 5-bromouracil.
D) double-strand breaks.

Question 11

Expansion of trinucleotide repeats can occur by

A) non-homologous end joining during double strand break repair
B) unequal crossing over during meiosis
C) DNA slippage during replication
D) B and C

Question 12

In human cells, pyrimidine dimers can be repaired by

A) photoreactivation.
B) nucleotide excision repair.
C) mismatch repair.
D) both A and B

Question 13

Translesion synthesis is mediated by

A) error-prone DNA polymerases
B) replicative DNA polymerases
C) DNA glycosylase
D) DNA photolyase

Question 14

Which DNA polymerase performs translesion synthesis past a thymine dimer by inserting
Two adenine residues?

A) DNA polymerase iota
B) DNA polymerase eta $\eta$
C) Both A and B
D) Neither A nor B; there are no error-free repair polymerases.

Question 15

Which statement is not true about the enzyme methyltransferase?

A) A sulfhydryl group of a cysteine residue in the enzyme accepts a methyl group.
B) The enzyme mediates direct reversal of DNA damage.
C) After accepting a methyl group from methylguanine, the enzyme can be used again.
D) The enzyme is present in organisms ranging from E. coli to humans.

Question 16

Steps in the base excision repair pathway occur in the following order:

A) Damaged base removal, endonuclease cleavage, nucleotide excision, repair synthesis ligation.
B) Endonuclease cleavage, damaged base removal, nucleotide excision, repair synthesis, ligation.
C) Damaged base removal, endonuclease cleavage, ligation, nucleotide excision, repair synthesis.
D) Endonuclease cleavage, damaged base removal, nucleotide excision, ligation, repair synthesis.

Question 17

The disease hereditary nonpolyposis colorectal cancer results from defects in which DNA
Repair pathway?

A) nucleotide excision repair
B) base excision repair
C) double-strand break repair
D) mismatch repair

Question 18

In the mismatch repair pathway, DNA damage is recognized by

A) RFC and PCNA
B) exonuclease EXO1
C) MutS
D) DNA polymerase

Question 19

The disease xeroderma pigmentosum (XP) is a rare autosomal recessive condition in humans. Individuals with this condition are extremely sensitive to UV light and nucleotide excision repair activity is reduced. When cell cultures from normal individuals and from XP patients are irradiated with various doses of UV light and cultured in radiolabeled thymidine…

A) cells from XP patients incorporate about the same amount of radiolabeled thymidine into their DNA as the cells from normal individuals.
B) cells from XP patients incorporate significantly less radiolabeled thymidine into their DNA.
C) cells from XP patients incorporate significantly more radiolabeled thymidine into their DNA.
D) neither cells from XP patients nor cells from normal individuals will incorporate radiolabeled thymindine into their DNA after UV irradiation.

Question 20

In mammalian cells double-strand breaks in DNA are primarily repaired by

A) nucleotide excision repair.
B) translesion synthesis.
C) homologous recombination.
D) nonhomologous end-joining.

Question 21

Which repair pathway requires a set of enzymes that recognize specific chemical modifications to DNA?

A) nucleotide excision repair
B) base excision repair
C) mismatch repair
D) non-homologous end joining

Question 22

Repair of a DNA double-strand break by homologous recombination is initiated by

A) the Mre11-Rad50-Nbs1 (MRN) complex.
B) the resolvasome.
C) Rad52.
D) BRCA1.

Question 23

Repair of a DNA double-strand break by nonhomologous end-joining is initiated by

A) the endonuclease Artemis.
B) Ku70 and Ku80.
C) DNA polymerase.
D) DNA-dependent protein kinase catalytic subunit.

Question 24

Homologous recombination repairs double-strand breaks by

A) direct ligation of DNA ends.
B) DNA synthesis without a template.
C) retrieving genetic information from an undamaged homologous chromosome.
D) translesion synthesis.

Question 25

Nonhomologous end-joing repairs double-strand breaks by

A) direct ligation of DNA ends.
B) DNA synthesis without a template.
C) retrieving genetic information from an undamaged homologous chromosome.
D) translesion synthesis.

Question 26

The Holliday junction is resolved into two duplexes by an enzyme complex called

A) DNA ligase
B) the resolvasome
C) Rad54
D) topoisomerase

Question 27

Explain why high-fidelity DNA replication is not always an advantage.

Question 28

Diagram how a point mutation changing a GC base pair to a GA base pair can be permanently incorporated by DNA replication.

Question 29

Compare and contrast silent mutations, missense mutations, nonsense mutations, and frameshift mutations.

Question 30

In addition to deploying repair machinery, cells respond to global DNA damage by preventing entry into S phase. Provide a rationale for this observation.

Question 31

Draw the structure of a cyclobutane ring between adjacent thymines and explain how formation of thymine-thymine dimers distorts the double helix.

Question 32

Compare and contrast the three major classes of DNA damage.

Question 33

Explain why unequal crossing over and DNA slippage results cause the specific problem of trinucleotide repeat expansion rather than random errors. Use diagrams to illustrate your answer.

Question 34

Define the term "translesion DNA synthesis" and briefly explain its mechanism.

Question 35

Explain why translesion synthesis is not truly a repair system.

Question 36

What two enzymes catalyze direct reversal of DNA damage? Diagram/briefly explain the mechanisms they use. Are both repair pathways present in human cells?

Question 37

Explain why repair of the methylated base O⁶-methylguanine by methyltransferases is considered very costly to a cell.

Question 38

Exposure of DNA to an oxidizing agent leads to the formation of 8-oxoguanine (oxoG). Name the pathway used to repair this damage and describe the two-step model based on X-ray crystallographic analysis for how the damage is first recognized.

Question 39

What is the mismatch repair system and when is it used? Include the key players of the system and the concept of strand discrimination in your answer.

Question 40

Describe the "molecular switch model" for MutS's mode of action. Include in your answer the proposed role of ATP.

Question 41

What process is defective in people with hereditary non-polyposis colon cancer? Explain your answer.

Question 42

Predict the molecular and phenotypic consequences of loss of strand discrimination by the mismatch repair pathway.

Question 43

What damage can be caused to DNA by UV irradiation? Describe the key steps of three different mechanisms by which this damage can be repaired. Do all three mechanisms repair the damage accurately? Are all mechanisms active in humans?

Question 44

How does transcription coupled repair (TCR) differ from global genome repair (GGR)?

Question 45

What DNA repair system is missing in xeroderma pigmentosum variant (XPV) patients? What is the backup system for lesions missed by the nucleotide excision repair system in XP-V patients?

Question 46

Compare and contrast repair of double strand breaks by homologous recombination or nonhomologous end-joining. Which is used predominantly in mammalian cells?

Question 47

Describe experiments that led to the characterization of the Holliday junction resolvasome.

Question 48

What would be the effect on reading frame and gene function if:
(a) Two nucleotides were inserted into the middle of an mRNA?
(b) Three nucleotides were inserted into the middle of an mRNA?
(c) One nucleotide was inserted into one codon and one subtracted from the next?
(d) A transition mutation occurs from GA during DNA replication? What is the effect after a second round of DNA replication?
(d) Exposure to an alkylating agent leads to the formation of O⁶-methylguanine? What is the effect after DNA replication?

Question 49

A friend of yours with xeroderma pigmentosum seeks your advice about participating in a sun tanning competition in Florida during Spring Break. Provide appropriate advice.

Question 50

Draw a diagram of a Holliday junction during double-strand break repair. Starting with that diagram, illustrate branch migration and resolution. Is the resulting DNA duplex "repaired" to its original state?

Question 51

You have isolated a novel protein factor you suspect is essential for efficient mismatch repair in mammalian cells. Design an experiment to test for repair activity in vitro. Show sample positive results.