Introduction: DNA replication (semi-conservative model) MCQs With Answer are essential for B. Pharm students preparing for exams and pharmacology applications. This concise guide covers core concepts such as the semi-conservative mechanism, replication fork dynamics, leading and lagging strand synthesis, DNA polymerases, primase, helicase, ligase, Okazaki fragments, proofreading, and replication origins. Understanding fidelity, replication enzymes, and experimental evidence (Meselson–Stahl) links molecular biology to drug targets and DNA-damaging therapies. These MCQs emphasize mechanism, enzyme function, regulation, and clinical relevance to strengthen problem-solving and concept retention. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What does the term “semi-conservative” replication mean?
- Each new DNA molecule contains two newly synthesized strands
- Each new DNA molecule contains one original strand and one newly synthesized strand
- The parent DNA is completely conserved and not separated
- DNA is synthesized from RNA templates
Correct Answer: Each new DNA molecule contains one original strand and one newly synthesized strand
Q2. Which classic experiment provided strong evidence for the semi-conservative model?
- Mendel’s pea plant crosses
- Meselson–Stahl density gradient experiment
- Hershey–Chase blender experiment
- Avery–MacLeod–McCarty transformation test
Correct Answer: Meselson–Stahl density gradient experiment
Q3. In which direction does DNA polymerase synthesize new DNA?
- 5′ to 3′ direction
- 3′ to 5′ direction
- Both 5’→3′ and 3’→5′ simultaneously
- Random direction depending on template
Correct Answer: 5′ to 3′ direction
Q4. Which enzyme unwinds the DNA double helix at the replication fork?
- DNA ligase
- Helicase
- Primase
- Topoisomerase
Correct Answer: Helicase
Q5. Which enzyme relieves supercoiling ahead of the replication fork?
- DNA polymerase
- Helicase
- Topoisomerase
- Primase
Correct Answer: Topoisomerase
Q6. What is the role of primase during replication?
- Degrades RNA primers after synthesis
- Synthesizes short RNA primers for DNA polymerase
- Joins Okazaki fragments
- Proofreads synthesized DNA
Correct Answer: Synthesizes short RNA primers for DNA polymerase
Q7. Which strand is synthesized continuously at the replication fork?
- Lagging strand
- Both strands equally
- Leading strand
- Template strand
Correct Answer: Leading strand
Q8. What are Okazaki fragments?
- Short DNA fragments on the lagging strand synthesized discontinuously
- Protein complexes that initiate replication
- RNA primers that start replication
- Supercoiled DNA regions ahead of fork
Correct Answer: Short DNA fragments on the lagging strand synthesized discontinuously
Q9. Which enzyme joins Okazaki fragments to form a continuous strand?
- DNA ligase
- DNA helicase
- Primase
- RNase H
Correct Answer: DNA ligase
Q10. Which activity provides proofreading during DNA replication?
- 5’→3′ polymerase activity
- 3’→5′ exonuclease activity of DNA polymerase
- RNase H removing primers
- Topoisomerase cutting strands
Correct Answer: 3’→5′ exonuclease activity of DNA polymerase
Q11. Which DNA polymerase performs bulk DNA synthesis in E. coli?
- DNA polymerase I
- DNA polymerase II
- DNA polymerase III
- Reverse transcriptase
Correct Answer: DNA polymerase III
Q12. What is the primary function of DNA polymerase I in bacteria?
- Main replicative polymerase for leading strand
- Removal of RNA primers and filling gaps (5’→3′ exonuclease)
- Helicase activity
- Origin recognition
Correct Answer: Removal of RNA primers and filling gaps (5’→3′ exonuclease)
Q13. Which protein increases DNA polymerase processivity by acting as a sliding clamp in bacteria?
- Helicase
- SSB (single-strand binding protein)
- β-clamp (sliding clamp)
- Topoisomerase
Correct Answer: β-clamp (sliding clamp)
Q14. Single-strand binding proteins (SSBs) function to:
- Seal nicks in DNA
- Bind and stabilize single-stranded DNA to prevent reannealing
- Synthesize RNA primers
- Cut supercoiled DNA
Correct Answer: Bind and stabilize single-stranded DNA to prevent reannealing
Q15. In eukaryotes, which polymerase primarily synthesizes the lagging strand?
- DNA polymerase α
- DNA polymerase δ
- DNA polymerase ε
- DNA polymerase I
Correct Answer: DNA polymerase δ
Q16. Which eukaryotic enzyme synthesizes RNA primers during replication?
- DNA polymerase δ
- Primase associated with DNA polymerase α
- DNA ligase I
- Topoisomerase II
Correct Answer: Primase associated with DNA polymerase α
Q17. What is the significance of the replication origin (ori) in DNA replication?
- It terminates replication
- Site where replication begins and replication proteins assemble
- Only found in eukaryotes
- Site where ribosomes bind
Correct Answer: Site where replication begins and replication proteins assemble
Q18. Which of the following best describes replication fork progression?
- Replication forks move only in one direction along the chromosome
- Replication forks are static while polymerases move randomly
- Replication forks progress bi-directionally from origins
- Replication occurs only at chromosome ends
Correct Answer: Replication forks progress bi-directionally from origins
Q19. How does RNase H contribute to replication?
- Synthesizes RNA primers
- Removes RNA primers hybridized to DNA
- Joins Okazaki fragments
- Unwinds DNA
Correct Answer: Removes RNA primers hybridized to DNA
Q20. Which chemical nucleotide analog is used to inhibit DNA polymerase and is relevant in chemotherapy?
- Ampicillin
- Aphidicolin
- Streptomycin
- Penicillin
Correct Answer: Aphidicolin
Q21. What determines the directionality (antiparallel nature) of the two DNA strands?
- Orientation of deoxyribose sugar phosphate backbone (5′ and 3′ ends)
- Base-pair composition only
- Helicase action exclusively
- Location of replication origins
Correct Answer: Orientation of deoxyribose sugar phosphate backbone (5′ and 3′ ends)
Q22. Which process directly increases replication fidelity by correcting mismatches after synthesis?
- Base excision repair
- Mismatch repair (MMR)
- Transcription-coupled repair
- Nucleotide addition by primase
Correct Answer: Mismatch repair (MMR)
Q23. Meselson and Stahl used which isotopes to distinguish parental and new DNA?
- 14C and 13C
- 32P and 33P
- 15N and 14N
- 2H and 1H
Correct Answer: 15N and 14N
Q24. What is the role of telomerase in eukaryotic DNA replication?
- Repairs double-strand breaks
- Extends telomeres to compensate for end-replication problem
- Removes RNA primers from Okazaki fragments
- Clamps polymerase to DNA
Correct Answer: Extends telomeres to compensate for end-replication problem
Q25. The end-replication problem primarily affects which part of the chromosome?
- Centromere
- Telomere (chromosome ends)
- Replication origin
- Introns only
Correct Answer: Telomere (chromosome ends)
Q26. Which antibiotic inhibits bacterial DNA gyrase (a type of topoisomerase)?
- Tetracycline
- Fluoroquinolones (e.g., ciprofloxacin)
- Chloramphenicol
- Aspirin
Correct Answer: Fluoroquinolones (e.g., ciprofloxacin)
Q27. What is the role of the origin recognition complex (ORC) in eukaryotes?
- Initiates replication by binding origins and recruiting replication factors
- Terminates replication
- Ligates Okazaki fragments
- Removes RNA primers
Correct Answer: Initiates replication by binding origins and recruiting replication factors
Q28. Which replicative polymerase has high fidelity and primarily synthesizes the leading strand in eukaryotes?
- DNA polymerase α
- DNA polymerase δ
- DNA polymerase ε
- DNA polymerase I
Correct Answer: DNA polymerase ε
Q29. Which factor loads the sliding clamp onto DNA in bacteria?
- Clamp loader complex (γ complex)
- Primase
- Topoisomerase
- DNA ligase
Correct Answer: Clamp loader complex (γ complex)
Q30. Which nucleotide triphosphate is NOT used by DNA polymerase during elongation?
- dATP
- dUTP
- dCTP
- dGTP
Correct Answer: dUTP
Q31. During replication, what is a replication bubble?
- A single-stranded gap left after replication
- A region where the double helix has separated and replication proceeds bidirectionally
- A protein that binds single-stranded DNA
- An RNA transcript from replication origin
Correct Answer: A region where the double helix has separated and replication proceeds bidirectionally
Q32. Which enzyme would be most directly inhibited by drugs that prevent Okazaki fragment ligation?
- DNA polymerase III
- DNA ligase
- Helicase
- Primase
Correct Answer: DNA ligase
Q33. What is the typical polarity of the template strand used by DNA polymerase?
- 5’→3′ polarity for the template
- 3’→5′ polarity for the template
- No polarity is required
- Both polarities simultaneously
Correct Answer: 3’→5′ polarity for the template
Q34. Which of the following increases the rate of replication fork movement?
- Depletion of dNTPs
- High processivity of DNA polymerase with sliding clamp
- Excess RNA primer removal
- Excessive supercoiling without topoisomerase
Correct Answer: High processivity of DNA polymerase with sliding clamp
Q35. Rolling-circle replication is commonly associated with which genetic element?
- Linear eukaryotic chromosomes
- Circular plasmids and some viruses
- Mitochondrial linear DNA exclusively
- Ribosomal RNA genes only
Correct Answer: Circular plasmids and some viruses
Q36. Which cellular phase is DNA replication confined to in eukaryotes?
- G1 phase
- S phase
- M phase
- G0 phase
Correct Answer: S phase
Q37. Which of the following best explains why DNA replication is semi-conservative rather than conservative?
- Because parental strands remain entirely together while new strands form separately
- Because each daughter duplex contains one parental and one newly synthesized strand
- Because parental strands are completely degraded and replaced
- Because DNA replication uses RNA intermediates exclusively
Correct Answer: Because each daughter duplex contains one parental and one newly synthesized strand
Q38. In Meselson–Stahl experiment, after one round of replication in light medium, what band was observed?
- Heavy (15N) band only
- Light (14N) band only
- Intermediate (hybrid) band only
- Two bands: heavy and light
Correct Answer: Intermediate (hybrid) band only
Q39. Which enzyme synthesizes DNA in the mitochondria?
- DNA polymerase γ (gamma)
- DNA polymerase α
- DNA polymerase I
- Reverse transcriptase
Correct Answer: DNA polymerase γ (gamma)
Q40. What is the consequence of defective 3’→5′ exonuclease activity in polymerases?
- Increased replication speed with no effect on fidelity
- Decreased replication fidelity and increased mutation rate
- No effect on replication
- Inability to synthesize RNA primers
Correct Answer: Decreased replication fidelity and increased mutation rate
Q41. Which feature distinguishes the lagging strand synthesis from leading strand synthesis?
- Requires continuous primer during replication
- Synthesized discontinuously as Okazaki fragments with multiple primers
- Only contains RNA bases
- Is synthesized in 3’→5′ direction
Correct Answer: Synthesized discontinuously as Okazaki fragments with multiple primers
Q42. Aphidicolin inhibits which class of enzymes?
- Ribonucleases
- DNA polymerases (eukaryotic replicative polymerases)
- Proteases
- Topoisomerases
Correct Answer: DNA polymerases (eukaryotic replicative polymerases)
Q43. Which nucleotide is used to initiate DNA synthesis by DNA polymerase?
- dGMP
- Free 3′-OH of existing primer (RNA primer)
- dTTP directly without primer
- dATP as monomer without primer
Correct Answer: Free 3′-OH of existing primer (RNA primer)
Q44. Which process is directly targeted by hydroxyurea as an anticancer agent?
- DNA ligation of Okazaki fragments
- Ribonucleotide reductase, reducing dNTP pools and slowing replication
- Topoisomerase II activity
- Helicase unwinding
Correct Answer: Ribonucleotide reductase, reducing dNTP pools and slowing replication
Q45. Which enzyme removes RNA primers in bacteria and simultaneously fills the gaps?
- DNA polymerase III holoenzyme
- DNA polymerase I (with 5’→3′ exonuclease activity)
- RNase P
- Ligase alone
Correct Answer: DNA polymerase I (with 5’→3′ exonuclease activity)
Q46. What role does the sliding clamp play in replication?
- Initiates primer synthesis
- Increases polymerase processivity by tethering polymerase to DNA
- Unwinds the DNA helix
- Removes RNA primers
Correct Answer: Increases polymerase processivity by tethering polymerase to DNA
Q47. Which statement about replication fidelity is correct?
- Fidelity depends only on base-pairing rules and nothing else
- Fidelity arises from nucleotide selectivity, proofreading exonuclease activity, and mismatch repair
- Fidelity is unimportant for cellular function
- Mismatch repair increases mutation rates
Correct Answer: Fidelity arises from nucleotide selectivity, proofreading exonuclease activity, and mismatch repair
Q48. What experimental method allowed separation of DNA based on density in the Meselson–Stahl experiment?
- Gel electrophoresis
- CsCl density gradient ultracentrifugation
- Spectrophotometry only
- Western blotting
Correct Answer: CsCl density gradient ultracentrifugation
Q49. In bacterial chromosomes, replication terminates at sites called:
- Telomeres
- oriC
- Ter sites
- Centromeres
Correct Answer: Ter sites
Q50. Which statement links DNA replication knowledge to pharmacology?
- Replication enzymes are irrelevant targets for antimicrobial or anticancer drugs
- Inhibitors of replication enzymes (polymerases, topoisomerases, ribonucleotide reductase) are used as antibiotics and chemotherapeutics
- All replication inhibitors are non-selective and unusable clinically
- Only RNA polymerase inhibitors affect DNA replication
Correct Answer: Inhibitors of replication enzymes (polymerases, topoisomerases, ribonucleotide reductase) are used as antibiotics and chemotherapeutics
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