MCQ Quiz: The Enzymes of DNA Metabolism

The complex processes of DNA replication, repair, and recombination are orchestrated by a precise cast of molecular machines—the enzymes of DNA metabolism. Understanding the specific roles of these proteins, from polymerases that build to ligases that seal, is fundamental to molecular biology and pharmacology. This quiz for PharmD students will test your knowledge of these critical enzymes and their functions in maintaining the integrity and fidelity of the genome.


1. Which enzyme is primarily responsible for synthesizing the new DNA strands during replication?

  • Helicase
  • Ligase
  • DNA Polymerase
  • Primase

Answer: DNA Polymerase


2. The function of DNA helicase in replication is to:

  • Synthesize RNA primers.
  • Join Okazaki fragments together.
  • Unwind the DNA double helix by breaking hydrogen bonds.
  • Relieve supercoiling ahead of the replication fork.

Answer: Unwind the DNA double helix by breaking hydrogen bonds.


3. DNA polymerase cannot initiate a new DNA strand on its own. It requires a short nucleic acid sequence with a free 3′-OH group, which is synthesized by which enzyme?

  • Ligase
  • Topoisomerase
  • Primase
  • Helicase

Answer: Primase


4. The lagging strand of DNA is synthesized discontinuously, creating short segments known as Okazaki fragments. Which enzyme is responsible for joining these fragments into a continuous strand?

  • DNA Polymerase I
  • Helicase
  • DNA Ligase
  • Primase

Answer: DNA Ligase


5. As DNA is unwound during replication, torsional stress and supercoiling build up ahead of the replication fork. Which class of enzymes relieves this strain?

  • Polymerases
  • Nucleases
  • Ligases
  • Topoisomerases

Answer: Topoisomerases


6. The “proofreading” function of DNA polymerase, which allows it to correct mismatched nucleotides, is due to its:

  • 5′ to 3′ polymerase activity.
  • 3′ to 5′ exonuclease activity.
  • Helicase activity.
  • Primase activity.

Answer: 3′ to 5′ exonuclease activity.


7. In E. coli, which DNA polymerase is the main replicative enzyme, responsible for synthesizing the leading and lagging strands?

  • DNA Polymerase I
  • DNA Polymerase II
  • DNA Polymerase III
  • DNA Polymerase IV

Answer: DNA Polymerase III


8. The role of DNA Polymerase I in E. coli replication is primarily to:

  • Unwind the DNA.
  • Synthesize the entire leading strand.
  • Remove the RNA primers and replace them with DNA.
  • Join the Okazaki fragments.

Answer: Remove the RNA primers and replace them with DNA.


9. The ends of linear eukaryotic chromosomes, known as telomeres, are maintained by which specialized enzyme?

  • DNA Polymerase δ
  • Helicase
  • Telomerase
  • DNA Ligase

Answer: Telomerase


10. Telomerase is a unique enzyme because it is a ribonucleoprotein that contains its own ________ template.

  • DNA
  • Protein
  • RNA
  • Lipid

Answer: RNA


11. In the process of base excision repair (BER), which enzyme is responsible for recognizing and removing a specific damaged base, like uracil from DNA?

  • AP Endonuclease
  • DNA Glycosylase
  • DNA Ligase
  • Photolyase

Answer: DNA Glycosylase


12. After a DNA glycosylase removes a damaged base, it leaves an “AP site” (apurinic/apyrimidinic site). Which enzyme then cuts the phosphodiester backbone at this site?

  • DNA Polymerase
  • Photolyase
  • Helicase
  • AP Endonuclease

Answer: AP Endonuclease


13. The chemotherapeutic agent etoposide is a topoisomerase inhibitor. It targets which specific enzyme, causing DNA strand breaks and cell death?

  • Topoisomerase I
  • Topoisomerase II
  • Helicase
  • DNA Ligase

Answer: Topoisomerase II


14. An enzyme that cuts one strand of the DNA double helix to relieve supercoiling is classified as a:

  • Type I Topoisomerase
  • Type II Topoisomerase
  • Helicase
  • Primase

Answer: Type I Topoisomerase


15. Which enzyme is responsible for repairing nicks in the phosphodiester backbone of DNA by forming a phosphodiester bond?

  • DNA Polymerase
  • DNA Ligase
  • Helicase
  • Primase

Answer: DNA Ligase


16. The “sliding clamp” (e.g., PCNA in eukaryotes) is a protein that:

  • Unwinds the DNA.
  • Synthesizes the RNA primer.
  • Increases the processivity of DNA polymerase, keeping it attached to the DNA strand.
  • Joins DNA fragments.

Answer: Increases the processivity of DNA polymerase, keeping it attached to the DNA strand.


17. In mismatch repair (MMR), enzymes must distinguish between the newly synthesized strand (containing the error) and the original template strand. In E. coli, this is accomplished by recognizing:

  • Nicks in the new strand.
  • The methylation status of the strands.
  • The length of the strands.
  • The direction of polymerase movement.

Answer: The methylation status of the strands.


18. Which of the following is NOT an enzyme directly involved in DNA replication?

  • Helicase
  • Primase
  • DNA Polymerase
  • RNA Polymerase

Answer: RNA Polymerase


19. The enzyme that uses light energy to repair pyrimidine dimers caused by UV radiation is called:

  • DNA Glycosylase
  • AP Endonuclease
  • DNA Photolyase
  • Excinuclease

Answer: DNA Photolyase


20. Nucleotide excision repair (NER) is a mechanism that repairs bulky DNA lesions. The enzyme complex that cuts the DNA strand on both sides of the lesion is called a(n):

  • Ligase
  • Polymerase
  • Excinuclease
  • Glycosylase

Answer: Excinuclease


21. The activity of many enzymes of DNA metabolism, such as polymerases and ligases, requires which ion as a cofactor?

  • Sodium (Na⁺)
  • Potassium (K⁺)
  • Magnesium (Mg²⁺)
  • Chloride (Cl⁻)

Answer: Magnesium (Mg²⁺)


22. A Type II Topoisomerase, like bacterial DNA gyrase, is unique because it:

  • Only cuts one strand of DNA.
  • Makes a transient double-strand break in the DNA.
  • Does not require ATP.
  • Only functions to increase supercoiling.

Answer: Makes a transient double-strand break in the DNA.


23. Fluoroquinolone antibiotics, like ciprofloxacin, work by inhibiting:

  • Eukaryotic topoisomerases.
  • Bacterial DNA gyrase (a type II topoisomerase).
  • DNA polymerase.
  • Helicase.

Answer: Bacterial DNA gyrase (a type II topoisomerase).


24. The function of single-strand binding (SSB) proteins in replication is to:

  • Synthesize the RNA primers.
  • Prevent the separated DNA strands from re-annealing.
  • Join the Okazaki fragments.
  • Provide the proofreading activity.

Answer: Prevent the separated DNA strands from re-annealing.


25. A key difference between DNA Polymerase I and DNA Polymerase III in E. coli is that:

  • Only Pol I has proofreading ability.
  • Pol III is the main replicative enzyme, while Pol I is primarily for repair and primer removal.
  • Only Pol I can synthesize DNA in the 5′ to 3′ direction.
  • Pol III has a slower catalytic rate than Pol I.

Answer: Pol III is the main replicative enzyme, while Pol I is primarily for repair and primer removal.


26. The enzyme “reverse transcriptase,” found in retroviruses like HIV, synthesizes:

  • RNA from a DNA template.
  • DNA from an RNA template.
  • Protein from an RNA template.
  • DNA from a protein template.

Answer: DNA from an RNA template.


27. The high fidelity of DNA replication is a result of:

  • The base-pairing rules (A with T, G with C).
  • The proofreading ability of DNA polymerase.
  • Post-replication mismatch repair systems.
  • All of the above.

Answer: All of the above.


28. An “exonuclease” is an enzyme that:

  • Cuts DNA at specific internal sites.
  • Removes nucleotides from the end of a DNA or RNA strand.
  • Joins two DNA strands together.
  • Synthesizes DNA.

Answer: Removes nucleotides from the end of a DNA or RNA strand.


29. An “endonuclease” is an enzyme that:

  • Only removes nucleotides from the 3′ end.
  • Cuts the phosphodiester backbone within a nucleic acid polymer.
  • Only removes nucleotides from the 5′ end.
  • Only acts on RNA.

Answer: Cuts the phosphodiester backbone within a nucleic acid polymer.


30. In eukaryotic replication, there are multiple DNA polymerases. The polymerase primarily responsible for synthesizing the lagging strand is:

  • Polymerase α
  • Polymerase β
  • Polymerase γ
  • Polymerase δ

Answer: Polymerase δ


31. The enzyme primarily responsible for replicating mitochondrial DNA is:

  • Polymerase α
  • Polymerase β
  • Polymerase γ
  • Polymerase δ

Answer: Polymerase γ


32. The processivity of a DNA polymerase refers to:

  • Its speed of synthesis.
  • Its accuracy.
  • The average number of nucleotides it adds before dissociating from the template.
  • Its ability to remove RNA primers.

Answer: The average number of nucleotides it adds before dissociating from the template.


33. The enzyme RecA in E. coli is a key protein involved in which process of DNA metabolism?

  • Initiation of replication.
  • Homologous recombination and DNA repair.
  • Termination of replication.
  • Primer synthesis.

Answer: Homologous recombination and DNA repair.


34. A key leadership role for a pharmacist in oncology is understanding how chemotherapeutics, like topoisomerase inhibitors, work by targeting:

  • Enzymes of DNA metabolism to induce cell death.
  • Signal transduction pathways.
  • Hormone receptors.
  • The cell membrane.

Answer: Enzymes of DNA metabolism to induce cell death.


35. A “business plan” for a new pharmacogenomics service would need to consider the role of enzymes like CYP450 in drug metabolism, which is distinct from the enzymes of:

  • DNA metabolism.
  • Protein synthesis.
  • Signal transduction.
  • Carbohydrate metabolism.

Answer: DNA metabolism.


36. A pharmacist’s knowledge of “human factors” is relevant when considering the complexity of chemotherapy regimens that target enzymes of DNA metabolism, as a dosing error can lead to:

  • Improved outcomes.
  • Severe toxicity.
  • No change in effect.
  • A mild side effect.

Answer: Severe toxicity.


37. The “forging ahead” mindset in pharmacy means embracing new technologies, like gene therapies, which may use enzymes to:

  • Correct or edit a patient’s DNA.
  • Dispense medications.
  • Manage pharmacy inventory.
  • Counsel patients.

Answer: Correct or edit a patient’s DNA.


38. The “regulation” of new drugs that target enzymes of DNA metabolism is the responsibility of the:

  • DEA
  • FDA
  • CMS
  • USP

Answer: The FDA


39. A “Clinical Decision Support” alert in an EHR would be crucial for a drug like a fluoroquinolone antibiotic to warn about:

  • Its interaction with dairy products.
  • Its potential to cause tendon rupture.
  • Its inhibition of bacterial DNA gyrase.
  • Both A and B.

Answer: Both A and B.


40. An “analytics and reporting system” could be used in oncology to track the use of:

  • Topoisomerase inhibitors.
  • Antimetabolites.
  • Alkylating agents.
  • All of the above.

Answer: All of the above.


41. The energy required for the action of DNA ligase to form a phosphodiester bond is supplied by:

  • GTP
  • CTP
  • ATP or NAD⁺
  • The hydrolysis of the DNA backbone.

Answer: ATP or NAD⁺


42. A “Klenow fragment” is a portion of which E. coli enzyme?

  • DNA Polymerase I
  • DNA Polymerase II
  • DNA Polymerase III
  • DNA Ligase

Answer: DNA Polymerase I


43. The “antidotal therapy” for methotrexate, an antimetabolite, is leucovorin, which works by:

  • Inhibiting an enzyme of DNA metabolism.
  • Bypassing the metabolic block caused by methotrexate.
  • Binding directly to the methotrexate.
  • Increasing the renal clearance of methotrexate.

Answer: Bypassing the metabolic block caused by methotrexate.


44. A key “policy” issue related to drugs targeting enzymes of DNA metabolism is:

  • The high cost of many newer oncology agents.
  • Their over-the-counter availability.
  • Their use in veterinary medicine.
  • Their lack of side effects.

Answer: The high cost of many newer oncology agents.


45. Which of the following is an example of an “endonuclease” involved in DNA repair?

  • DNA Polymerase
  • AP Endonuclease
  • DNA Ligase
  • Helicase

Answer: AP Endonuclease


46. A “human resources” consideration for an oncology pharmacy is ensuring that staff are properly trained on the safe handling of drugs that target enzymes of DNA metabolism, as they are often:

  • Harmless.
  • Hazardous and carcinogenic.
  • Volatile.
  • Inexpensive.

Answer: Hazardous and carcinogenic.


47. A “negotiation” with a payer might be necessary to gain approval for a new, expensive drug that targets a specific enzyme of DNA metabolism. The pharmacist’s strongest argument would be based on:

  • Evidence of improved clinical outcomes.
  • The drug’s novel mechanism.
  • The high price of the drug.
  • Patient preference alone.

Answer: Evidence of improved clinical outcomes.


48. In which “practice setting” is a pharmacist most likely to manage chemotherapy regimens that target enzymes of DNA metabolism?

  • Community pharmacy
  • Oncology clinic or hospital
  • Mail-order pharmacy
  • Supermarket pharmacy

Answer: Oncology clinic or hospital


49. The “services” a clinical pharmacist provides in oncology include:

  • Calculating chemotherapy doses.
  • Managing the toxicities of drugs that target DNA metabolism enzymes.
  • Educating patients on their therapy.
  • All of the above.

Answer: All of the above.


50. The ultimate principle of why we study the enzymes of DNA metabolism in pharmacy is because they are:

  • Easy to understand.
  • Frequent and critical targets for a wide range of antimicrobial and antineoplastic drugs.
  • Not relevant to drug therapy.
  • Only important for basic science research.

Answer: Frequent and critical targets for a wide range of antimicrobial and antineoplastic drugs.

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