Molecular Biology and Genomics Practice Questions

Q: Which of the following is NOT true about post-transcriptional modification of RNA?

Glycosylation. **Explanation:** Post-transcriptional modifications are chemical alterations that convert a primary RNA transcript (hnRNA) into a functional mature mRNA molecule. This process occurs exclusively in the **nucleus** of eukaryotes. **Why Glycosylation is the correct answer:** **Glycosylation** is a **post-translational modification**, not post-transcriptional. It involves the addition of carbohydrate chains to proteins (forming glycoproteins) and occurs in the **Endoplasmic Reticulum (ER) and Golgi apparatus**. It is essential for protein folding, stability, and cell signaling, but it has no role in RNA processing. **Why the other options are incorrect (Post-transcriptional processes):** * **5' Capping (Option A):** Addition of 7-methylguanosine to the 5' end via a 5'-5' triphosphate linkage. It protects mRNA from exonucleases and is vital for translation initiation. * **Addition of poly A tail (Option B):** Polyadenylation involves adding ~200 adenine residues to the 3' end by the enzyme Poly(A) Polymerase. This regulates mRNA stability and nuclear export. * **Removal of introns (Option C):** Splicing removes non-coding sequences (introns) and joins coding sequences (exons) together, catalyzed by the spliceosome (snRNPs). **High-Yield Clinical Pearls for NEET-PG:** * **RNA Editing:** Another form of post-transcriptional modification (e.g., ApoB-100 in liver vs. ApoB-48 in intestine via C-to-U editing). * **Splicing Inhibitors:** Antibodies against snRNPs (Anti-Smith antibodies) are highly specific for **Systemic Lupus Erythematosus (SLE)**. * **Mushroom Poisoning:** $\alpha$-amanitin (from *Amanita phalloides*) inhibits **RNA Polymerase II**, blocking mRNA synthesis.

Q: What are nucleosomes composed of?

DNA and Histones. ### Explanation **1. Why the Correct Answer is Right:** A **nucleosome** is the fundamental structural unit of chromatin, often described as "beads on a string." It consists of a segment of **DNA** (approximately 147 base pairs) wrapped 1.65 times around a protein core called the **histone octamer**. This octamer is composed of two copies each of four core histones: **H2A, H2B, H3, and H4**. The DNA is negatively charged (due to phosphate groups), while histones are positively charged (rich in Lysine and Arginine), allowing for a tight electrostatic bond that facilitates DNA packaging within the nucleus. **2. Why the Other Options are Wrong:** * **Option A & C:** RNA is not a structural component of the nucleosome core. While RNA is involved in transcription and regulation, the nucleosome is strictly a DNA-protein complex. * **Option D:** Although RNA may be present in the overall chromatin environment during transcription, it is not a constituent of the nucleosome unit itself. **3. NEET-PG High-Yield Facts & Clinical Pearls:** * **Linker Histone:** **Histone H1** is known as the "linker histone." It sits outside the nucleosome core and helps stabilize the 30-nm chromatin fiber. It is *not* part of the octamer. * **Epigenetics:** Acetylation of histones (by HATs) neutralizes their positive charge, relaxing chromatin (**Euchromatin**) and increasing transcription. Deacetylation (by HDACs) leads to condensed **Heterochromatin** and gene silencing. * **Drug Link:** Sodium valproate (anti-epileptic) acts as a Histone Deacetylase (HDAC) inhibitor. * **Amino Acid Richness:** Histones are exceptionally rich in **Lysine and Arginine**, which is a frequent MCQ point regarding their basic nature.

Q: Maternal disomy of chromosome 15 is seen in which genetic syndrome?

Prader-Willi syndrome. This question tests your knowledge of **Genomic Imprinting** and **Uniparental Disomy (UPD)**, high-yield concepts for NEET-PG. ### **Explanation of the Correct Answer** **Prader-Willi Syndrome (PWS)** occurs due to the loss of expression of genes on the **paternally derived** chromosome 15 (specifically the 15q11-q13 region). While the most common cause is a paternal deletion (70%), the second most common cause (25%) is **Maternal Uniparental Disomy**. In maternal UPD, the child inherits two copies of chromosome 15 from the mother and none from the father. Since the maternal copies are "silenced" (imprinted) in this specific region, the child lacks the necessary active paternal genes, leading to the PWS phenotype. ### **Analysis of Incorrect Options** * **Angelman Syndrome:** This is the "sister" syndrome to PWS. It results from the loss of the **maternally** derived 15q11-q13 region (specifically the *UBE3A* gene). It is caused by maternal deletion or **Paternal Disomy**. * **Klinefelter's Syndrome:** A chromosomal aneuploidy characterized by a **47, XXY** karyotype. It is not related to imprinting or UPD. * **Turner's Syndrome:** A chromosomal aneuploidy characterized by a **45, XO** karyotype (monosomy X). ### **NEET-PG High-Yield Clinical Pearls** * **Prader-Willi Presentation:** Infantile hypotonia, feeding difficulties initially followed by **hyperphagia and obesity**, hypogonadism, and small hands/feet. * **Angelman Presentation:** "Happy Puppet" syndrome—inappropriate laughter, ataxia, seizures, and severe intellectual disability. * **Mnemonic:** **P**rader-Willi = **P**aternal deletion / **M**aternal Disomy. **A**ngelman = **M**aternal deletion / **P**aternal Disomy. (Remember: **P**ader = **P**op/Paternal; **A**ngelman = **M**om/Maternal).

Q: In which phase of the cell cycle does proofreading occur?

S. **Explanation:** **Why S Phase is Correct:** DNA replication occurs exclusively during the **S (Synthesis) phase** of the cell cycle. Proofreading is an intrinsic function of **DNA Polymerases** (specifically Pol $\delta$ and Pol $\epsilon$ in eukaryotes), which possess **3' to 5' exonuclease activity**. This activity allows the enzyme to immediately identify, remove, and replace mismatched nucleotides as they are being incorporated. Since proofreading is a "real-time" correction mechanism coupled with DNA synthesis, it must occur during the S phase. **Why Other Options are Incorrect:** * **G1 Phase:** This is a pre-synthetic gap phase focused on cell growth and preparation for DNA replication. No new DNA is synthesized here, so proofreading does not occur. * **G2 Phase:** This is the post-synthetic gap phase. While **Mismatch Repair (MMR)** and other repair mechanisms (like homologous recombination) are active here to fix errors missed during replication, the specific process of "proofreading" by DNA polymerase has already concluded. * **M Phase:** This is the Mitosis phase where sister chromatids segregate. The DNA is highly condensed into chromosomes, making it inaccessible for replication-linked proofreading. **NEET-PG High-Yield Pearls:** * **Proofreading Direction:** Always **3' $\rightarrow$ 5' exonuclease activity**. * **Synthesis Direction:** Always **5' $\rightarrow$ 3' polymerase activity**. * **Clinical Correlation:** Defects in **Mismatch Repair (MMR)**—which acts as a "spell-check" after proofreading—lead to **Lynch Syndrome (HNPCC)**, characterized by microsatellite instability. * **Key Enzyme:** In eukaryotes, **DNA Polymerase $\gamma$** is responsible for proofreading mitochondrial DNA.

Q: A 7-year-old child of short stature presents with skin patches and learning difficulties. Diagnostic workup indicates a defect in DNA repair specifically related to double-strand breaks. What is the most likely diagnosis?

Bloom Syndrome. ***Bloom Syndrome***- This condition is caused by a mutation in the **BLM gene**, which encodes a **RecQ helicase** necessary for homologous recombination repair (a mechanism for **double-strand break** repair), consistent with the clinical presentation.- Key clinical features include **short stature**, **telangiectatic erythema** (skin patches, especially on sun exposure), and intellectual disability/learning difficulties. *Xeroderma Pigmentosum*- This disease results from a defect in **Nucleotide Excision Repair (NER)**, crucial for repairing DNA damage caused by UV light (e.g., pyrimidine dimers), not primarily double-strand breaks.- Patients exhibit extreme **photosensitivity** and have a drastically increased risk of developing multiple skin cancers early in life.*Cockayne Syndrome*- Cockayne syndrome results from defects in genes like *ERCC8* or *ERCC6*, impairing **Transcription-Coupled Repair (TCR)**, a specific type of NER.- While it presents with short stature (often described as **cachectic dwarfism**) and neurological defects, the primary DNA defect is not in the repair of double-strand breaks but rather UV adducts in transcribed DNA.*Lynch Syndrome*- Also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), this syndrome is caused by defects in **Mismatch Repair (MMR)** genes (e.g., *MLH1*, *MSH2*).- It primarily predisposes individuals to colorectal and endometrial cancers and is not typically associated with the features of short stature and specific DNA double-strand break repair defects seen in this child.

Q: Which of the following enzymes is responsible for the immortality of cancer cells?

Telomerase. ***Telomerase*** **Telomerase** is a **ribonucleoprotein enzyme** that adds repetitive DNA sequences (TTAGGG) to the ends of chromosomes (**telomeres**), counteracting the natural shortening that occurs during cell division. The activation of **telomerase** is characteristic of most cancer cells, granting them the ability to divide indefinitely, fulfilling the hallmark of **unlimited replicative potential** (immortality). *Topoisomerase* This enzyme is crucial for relieving the **torsional strain** (supercoiling) in the DNA helix that arises ahead of the replication fork or during transcription. Its primary role is managing DNA structure and integrity, not determining cellular lifespan or **immortality** through **telomere** maintenance. *Helicase* **Helicases** are motor proteins that use energy from ATP hydrolysis to **unwind nucleic acid duplexes** (like the DNA double helix) in fundamental processes such as DNA replication, repair, and transcription. While essential for replication, it does not prevent the gradual loss of terminal DNA sequences (**telomeres**) required for cancer cell immortality. *RNA polymerase* This enzyme is responsible for **transcription**, the process of synthesizing an **RNA molecule** from a DNA template. Its function is focused on gene expression (protein synthesis) and is not directly involved in maintaining the length of **telomeres** or conferring replicative immortality upon cells.

Q: A patient presents with multiple colonic polyps and has been diagnosed with colorectal carcinoma. There is a strong family history of Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Which DNA repair mechanism is most likely defective in this condition?

Mismatch repair. ***Mismatch repair***- **HNPCC (Lynch syndrome)** is caused by inherited germline mutations in genes (e.g., *MLH1*, *MSH2*) that are responsible for the **mismatch repair (MMR)** pathway. - The failure of MMR leads to the accumulation of errors, specifically in repetitive DNA sequences, resulting in **microsatellite instability** which drives carcinogenesis.*Nucleotide excision repair*- This mechanism repairs bulky helix-distorting lesions in DNA, most commonly **pyrimidine dimers** caused by UV radiation. - A classic disease associated with defective **NER** is **Xeroderma Pigmentosum**, which presents with extreme sun sensitivity and a high risk of skin cancers.*Base excision repair*- This pathway primarily corrects small, non-helix distorting damage, such as oxidized or alkylated bases, utilizing enzymes like **DNA glycosylases**.- While fundamental for DNA maintenance, primary defects in BER are not the underlying cause of pathogenesis in **Lynch syndrome**.*Double-strand break repair*- This mechanism repairs severe damage where the entire DNA helix is broken, typically via **Homologous Recombination (HR)** or **Non-Homologous End Joining (NHEJ)**. - Defects in HR are often linked to hereditary breast and ovarian cancers (e.g., *BRCA1*/ *BRCA2* mutations) and are distinct from the pathogenesis of **HNPCC**.

Question 1

Which of the following is NOT true about post-transcriptional modification of RNA?

Accepted Answer

Glycosylation

Answer

5' Capping

Answer

Addition of poly A tail

Answer

Removal of introns

Question 2

A codon codes for a single amino acid. This characteristic is called?

Accepted Answer

Unambiguous

Answer

Non-overlapping

Answer

Non-punctate

Answer

Degeneracy

Question 3

What are nucleosomes composed of?

Accepted Answer

DNA and Histones

Answer

DNA and RNA

Answer

RNA and Histones

Answer

DNA, RNA, and Histones

Question 4

Maternal disomy of chromosome 15 is seen in which genetic syndrome?

Accepted Answer

Prader-Willi syndrome

Answer

Klinefelter's syndrome

Answer

Angelman syndrome

Answer

Turner's syndrome

Question 5

Which enzyme is associated with the aging process related to DNA?

Accepted Answer

Telomerase

Answer

Telosomerase

Answer

Topoisomerase

Answer

DNA polymerase

Question 6

What is true about crossing over?

Accepted Answer

Occurs between non-sister chromatids of homologous chromosomes

Answer

Occurs during the diplotene stage

Answer

Occurs between sister chromatids of homologous chromosomes

Answer

Occurs between sister chromatids of non-homologous chromosomes

Question 7

In which phase of the cell cycle does proofreading occur?

Accepted Answer

S

Answer

G1

Answer

G2

Answer

M

Question 8

A 7-year-old child of short stature presents with skin patches and learning difficulties. Diagnostic workup indicates a defect in DNA repair specifically related to double-strand breaks. What is the most likely diagnosis?

Accepted Answer

Bloom Syndrome

Answer

Lynch Syndrome

Answer

Xeroderma Pigmentosum

Answer

Cockayne Syndrome

Question 9

Which of the following enzymes is responsible for the immortality of cancer cells?

Accepted Answer

Telomerase

Answer

RNA polymerase

Answer

Helicase

Answer

Topoisomerase

Question 10

A patient presents with multiple colonic polyps and has been diagnosed with colorectal carcinoma. There is a strong family history of Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Which DNA repair mechanism is most likely defective in this condition?

Accepted Answer

Mismatch repair

Answer

Double-strand break repair

Answer

Nucleotide excision repair

Answer

Base excision repair

Molecular Biology and Genomics — MCQs

Molecular Biology and Genomics — MCQs

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