Molecular Biology (DNA Replication, Repair, Transcription, Translation) MCQs

Biochemistry · 76 free questions with answers & explanations.

1. A 30-year-old man with xeroderma pigmentosum (XP) has extreme ultraviolet radiation sensitivity and multiple skin cancers. The molecular mechanism underlying XP most commonly involves a defect in:
2. In eukaryotic mRNA processing, the 5' cap added co-transcriptionally is composed of:
3. A cancer cell develops resistance to methotrexate through amplification of the DHFR gene. Which process of DNA replication is most analogous to gene amplification in terms of mechanism?
4. An antibiotic inhibits peptidyl transferase activity and causes premature release of incomplete peptide chains during translation. This antibiotic is most likely:
5. Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is caused by germline mutations in genes encoding proteins of the mismatch repair (MMR) system. The hallmark molecular finding in MMR-deficient tumors is:
6. Xeroderma pigmentosum (XP) patients develop multiple skin cancers with minimal UV exposure. Cells from classic XP fail to remove pyrimidine dimers formed by UV radiation. The DNA repair pathway that is specifically defective in XP is:
7. During eukaryotic translation, the aminoacyl-tRNA that decodes a particular codon is recognized by the ribosome via codon-anticodon base pairing at the A site. After peptide bond formation, translocation moves the ribosome by one codon. Which GTPase is required for the translocation step in eukaryotes?
8. Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) results from germline mutations in mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, or PMS2. The biochemical hallmark of MMR deficiency in tumor tissue is:
9. RNA splicing removes introns from pre-mRNA via a two-step transesterification reaction. In the first step, the 2'-OH of the branch point adenosine attacks the 5' splice site, forming a lariat intermediate. Mutations in the invariant GU dinucleotide at the 5' splice site would MOST likely result in:
10. Xeroderma pigmentosum (XP) patients have extreme UV sensitivity and very high rates of skin cancers. XP complementation group A (XPA) involves a protein that recognizes bulky DNA adducts. Which DNA repair pathway is defective in XP?
11. A missense mutation changes the 5' splice donor site (GT→AT) of an exon-intron junction in a gene. Which consequence on the mRNA is most likely?
12. Aminoacyl-tRNA synthetases are responsible for charging tRNAs. Which unique feature ensures that the genetic code is accurately implemented (the 'second genetic code')?
13. Telomere shortening is proposed as a mechanism of cellular senescence. Telomerase uses an internal RNA template to add TTAGGG repeats. In which cells is telomerase constitutively active?
14. Which of the following best describes the role of the Shine-Dalgarno sequence in prokaryotic translation initiation?
15. Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair (NER). XP complementation group A (XPA) protein functions as a damage recognition scaffold. A patient in complementation group D has a mutation in the XPD/ERCC2 gene, which encodes a helicase subunit of the TFIIH complex. This mutation causes XP but also features of Cockayne syndrome (neurodegeneration). Why does XPD mutation affect transcription-coupled NER more severely than global genome NER?
16. During eukaryotic translation, the 80S ribosome dissociates after termination. Eukaryotic release factor eRF1 recognizes all three stop codons (UAA, UAG, UGA). eRF3 is a GTPase. After peptide release, the ribosome recycling factor equivalent in eukaryotes is ABCE1. Which post-termination event does ABCE1 catalyze using ATP hydrolysis?
17. CRISPR-Cas9 genome editing uses a single guide RNA (sgRNA) that base-pairs with the target DNA. The Cas9 nuclease requires a PAM (protospacer adjacent motif) sequence on the non-template strand for target recognition. The most widely used Streptococcus pyogenes Cas9 uses which PAM sequence?
18. A somatic mutation in the mismatch repair gene MLH1 leads to microsatellite instability (MSI) in a colon cancer patient. Lynch syndrome (hereditary) involves germline MMR mutations. Mismatch repair corrects base mismatches and insertion-deletion loops after replication. Which strand is recognized as the 'parental' strand to direct MMR to correct the newly synthesized strand in eukaryotes?
19. In Western blotting, a laboratory technician uses an anti-phosphoserine antibody to detect a 52 kDa phosphoprotein. The membrane shows no band despite positive controls working. Which troubleshooting step specifically addresses the risk of phosphatase activity dephosphorylating the target during sample preparation?
20. A cell from a patient with Xeroderma pigmentosum is irradiated with UV light. The predominant DNA lesion formed and the specific repair mechanism that is defective in this disease are:
21. During RNA polymerase II-mediated mRNA transcription in eukaryotes, the heptapeptide repeat domain (CTD) of RNA Pol II large subunit must be phosphorylated at serine-5 for which step, and at serine-2 for which step?
22. In eukaryotic translation, which initiation factor is responsible for scanning the 5' UTR from the 5' cap to locate the AUG start codon, and what feature of the mRNA context (Kozak sequence) determines start codon efficiency?
23. Hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome) results from germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2). The diagnostic hallmark on tumor tissue analysis is:
24. A patient has Ataxia-Telangiectasia (A-T). The mutated gene ATM encodes a kinase that responds to double-strand breaks (DSBs). Which histone modification occurs immediately at DSB sites and serves as the earliest molecular marker used to detect and quantify DSBs?
25. Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). Patients develop extreme photosensitivity and skin cancers. In NER, which step is specifically defective in the most common XP complementation group (XP-C)?
26. A 28-year-old woman with Lynch syndrome (HNPCC) carries a germline mutation in MLH1. This gene encodes a mismatch repair (MMR) protein. Which type of mutation is most uniquely generated when MMR is defective, and what is the molecular signature it creates?
27. In eukaryotic translation, a 5' cap-independent mechanism operates via internal ribosome entry sites (IRES) to allow translation of certain mRNAs under stress. Which of the following cellular conditions specifically upregulates IRES-mediated translation while global cap-dependent translation is suppressed?
28. A pharmaceutical company develops a splice-switching antisense oligonucleotide (ASO) that corrects aberrant splicing of the SMN2 pre-mRNA to produce full-length SMN protein, used in spinal muscular atrophy (SMA). What is the mechanism of action of this ASO at the molecular level?
29. Telomerase adds hexanucleotide repeats (TTAGGG) to chromosomal ends to prevent replicative senescence. In which of the following scenarios is telomerase activity pathologically re-activated?
30. During eukaryotic DNA replication, the replication fork moves 5'→3' on both strands, yet DNA polymerase can only synthesize in the 5'→3' direction. Which of the following correctly describes the molecular resolution of this apparent paradox on the lagging strand?
31. Nucleotide excision repair (NER) corrects bulky helix-distorting lesions such as pyrimidine dimers. In global genome NER, which protein complex first recognises the lesion, and what is the significance of XPC mutations?
32. A class of antibiotics inhibits the 50S ribosomal subunit by blocking peptidyl transferase activity, causing premature chain termination when they insert into the A site and accept the growing peptide chain from P-site tRNA (producing truncated peptidyl-aminoacyl adducts). This describes the mechanism of:
33. Post-translational modification of histones plays a central role in chromatin remodelling. Trimethylation of histone H3 at lysine 4 (H3K4me3) is associated with active gene transcription, whereas trimethylation at H3K27 is associated with repression. Which enzyme complex catalyses H3K27 trimethylation and thereby maintains transcriptional silencing of developmental genes?
34. During translation of a eukaryotic mRNA, the 43S pre-initiation complex scans from the 5' cap toward the start codon. When the anticodon of Met-tRNAi recognises the AUG start codon, a GTP hydrolysis event catalysed by which factor triggers release of eIFs and allows 60S subunit joining?
35. Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). Which type of DNA lesion is primarily targeted by NER that is NOT repaired by base excision repair (BER)?
36. During eukaryotic mRNA processing, which modification prevents exonuclease degradation of the 5' end of pre-mRNA?
37. In Cockayne syndrome, DNA repair is defective specifically for transcription-coupled NER (TC-NER). What is the clinical phenotype compared to classic XP (global-genome NER defect)?
38. Which translation termination mechanism is exploited by aminoglycoside antibiotics (e.g., gentamicin) causing readthrough therapy potential in premature stop codon diseases?
39. Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair (NER). The specific type of DNA damage that NER corrects, and which is caused by UV radiation, is:
40. In eukaryotic translation, the cap-dependent initiation complex assembles at the 5' m7G cap. The critical eIF (eukaryotic initiation factor) that scans the mRNA in the 5' to 3' direction and recognises the Kozak consensus sequence around the AUG start codon is:
41. A child with recurrent bacterial and viral infections is found to have absent lymphocytes and absent adenosine deaminase (ADA) activity. Deoxyadenosine accumulates intracellularly in lymphocytes, and dATP pools become massively elevated. The primary mechanism by which elevated dATP causes lymphocyte death is:
42. Lynch syndrome (hereditary non-polyposis colorectal cancer) results from germline mutations in DNA mismatch repair (MMR) genes. MSH2 and MLH1 account for the majority of cases. The consequence of defective MMR detectable in laboratory testing is:
43. Xeroderma pigmentosum is caused by defective nucleotide excision repair (NER). Which type of DNA lesion does NER specifically recognize and repair, and which is the rate-limiting step?
44. During translation, aminoacyl-tRNA is delivered to the ribosome A-site by which elongation factor, and what energy source drives this step?
45. Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair (NER). Which specific step of NER is defective in the most common form (XP-C)?
46. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. The mature miRNA strand is incorporated into the RISC complex. What is the MECHANISM of miRNA-mediated gene silencing when the miRNA has partial complementarity to the target mRNA?
47. Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). Which of the following correctly describes the step in NER that is specifically defective in XPC-deficient patients?
48. A drug inhibits topoisomerase II by stabilising the cleavable complex (enzyme-DNA covalent intermediate), preventing strand religation. Which class of anticancer agent acts by this mechanism?
49. The spliceosome removes introns from pre-mRNA. Which RNA component of the spliceosome catalyses the transesterification reactions during splicing?
50. Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair (NER). The most mutation-prone dimers in XP are caused by:
51. MicroRNAs (miRNAs) silence gene expression post-transcriptionally. The mechanism involves:
52. In eukaryotic mRNA processing, which modification protects the mRNA from 5' exonuclease degradation and is required for ribosomal cap-dependent translation initiation?
53. Nucleotide excision repair (NER) is defective in xeroderma pigmentosum (XP). NER specifically recognises and removes which type of DNA lesion?
54. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. Which mechanism describes how miRNAs most commonly silence target mRNA expression in mammalian cells?
55. In eukaryotic transcription, RNA polymerase II transcribes mRNA precursors. Which covalent modification of the CTD (C-terminal domain) of RNA Pol II switches it from the promoter-bound preinitiation state to productive elongation?
56. Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). The primary DNA lesion that NER corrects, formed by UV radiation, is:
57. In translation, the process of 'wobble' at the third codon position explains why the genetic code is degenerate. Wobble occurs because:
58. CRISPR-Cas9 gene editing uses a guide RNA (gRNA) to direct Cas9 nuclease to cleave a target DNA sequence. A mandatory requirement for Cas9 cleavage adjacent to the target site is the presence of:
59. A patient with xeroderma pigmentosum (XP) has an extreme predisposition to UV-induced skin cancer. The biochemical defect involves failure of which DNA repair pathway?
60. Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is caused by germline mutations in mismatch repair (MMR) genes. The molecular hallmark detectable in tumour tissue is:
61. During eukaryotic mRNA processing, the 5' cap is added to the nascent mRNA. The 5' cap structure is:
62. Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). XP patients develop skin cancers on sun-exposed areas. In global genome NER (GG-NER), the initial damage recognition step involves which molecular complex?
63. Aminoacyl-tRNA synthetases (aaRS) ensure the fidelity of translation by covalently attaching the correct amino acid to its cognate tRNA. The 'editing/proofreading' mechanism of class I aaRS involves:
64. Nucleotide excision repair (NER) is defective in xeroderma pigmentosum (XP). NER removes bulky adducts (from UV) by a cut-and-patch mechanism. The FIRST recognition step in global genome NER (GGR) is performed by:
65. A patient with a heterozygous nonsense mutation in a tumor suppressor gene has residual mRNA from the mutant allele that contains a premature termination codon (PTC). The cellular quality control mechanism that degrades this abnormal mRNA is:
66. Nucleotide excision repair (NER) corrects bulky DNA adducts caused by UV radiation (cyclobutane pyrimidine dimers). Which genetic disorder results from defective NER, presenting with extreme photosensitivity, skin cancer, and neurological degeneration?
67. RNA polymerase II transcribes protein-coding mRNA. The C-terminal domain (CTD) of its largest subunit is extensively phosphorylated during transition from transcription initiation to elongation. Phosphorylation of Ser5 and Ser2 of the heptapeptide CTD repeat serves as a landing platform for which processes?
68. Protein folding in the ER is assisted by molecular chaperones. Accumulation of misfolded proteins in the ER triggers the unfolded protein response (UPR). Which ER transmembrane sensor activates XBP1 mRNA splicing (non-canonical splicing) as part of UPR?
69. Xeroderma pigmentosum is caused by defective nucleotide excision repair (NER). The specific step that is deficient is:
70. Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNAs containing:
71. The lac operon in E. coli is under dual regulation. Which combination of conditions leads to maximal transcription of the lac operon?
72. During DNA replication in eukaryotes, synthesis of the lagging strand requires repeated priming by RNA primase. After primer removal by RNase H and Pol delta, the resulting nicks are sealed. Which enzyme is responsible for joining the Okazaki fragments by sealing single-strand nicks in DNA?
73. A 25-year-old woman is diagnosed with chronic myeloid leukemia (CML). Cytogenetics reveals the Philadelphia chromosome — a reciprocal translocation between chromosomes 9 and 22, creating the BCR-ABL fusion gene. The resulting chimeric oncoprotein has constitutively active tyrosine kinase activity. Imatinib blocks this kinase. At the molecular level, imatinib is best classified as which type of inhibitor?
74. A researcher is studying a mutant gene where the codon AAA (lysine) has been changed to UAA at position 150 of a 400-amino-acid protein. The resulting protein is only 149 amino acids long. Which type of mutation has occurred?
75. During transcription in eukaryotes, RNA polymerase II requires a set of general transcription factors (GTFs) to assemble at the promoter. Which GTF is responsible for recognizing and binding the TATA box sequence in the promoter, and which subunit of this factor directly contacts DNA?
76. A genetic laboratory reports that a patient's PCR-amplified DNA fragment shows a pattern consistent with heterozygosity for a point mutation. On Sanger sequencing, the trace shows two overlapping peaks at the position of interest, one representing guanine (G) and one representing adenine (A). This finding indicates that the patient is heterozygous for which type of mutation if the original codon is GGA (glycine) and the mutant allele reads AGA?