Molecular Biology and Genomics

Molecular Biology and Genomics Indian Medical PG Question 1: Which RNA modification at the 3' end stabilizes mRNA by preventing exonuclease degradation?

• A. Polyadenylation (Correct Answer)
• B. Capping
• C. Splicing
• D. Methylation

Molecular Biology and Genomics Explanation: ***Polyadenylation*** - The addition of a **poly-A tail** (a long chain of adenine nucleotides) to the **3' end** of mRNA is the primary modification that protects it from degradation by **3' to 5' exonucleases**. - This tail also plays crucial roles in mRNA export from the nucleus, translation initiation, and determining mRNA half-life. - The poly-A tail is progressively shortened by deadenylases, and once critically shortened, the mRNA becomes susceptible to degradation. *Capping* - **5' capping** involves the addition of a **7-methylguanosine cap** to the **5' end** of mRNA. - While this protects mRNA from **5' to 3' exonuclease** degradation, the question specifically asks about the **3' end** modification, which is polyadenylation. - The cap structure is also essential for ribosome binding and translation initiation. *Splicing* - **Splicing** is the process of removing **introns** (non-coding regions) and joining **exons** (coding regions) in pre-mRNA. - Its main function is to produce a mature mRNA sequence that can be translated into a functional protein, not to directly prevent exonuclease degradation. *Methylation* - **Methylation** can occur on various nucleotides within RNA molecules (e.g., N6-methyladenosine or m6A). - While methylation can influence mRNA stability, translation efficiency, and splicing, it is primarily a regulatory modification rather than a direct structural protection against exonuclease degradation like polyadenylation.

Molecular Biology and Genomics Indian Medical PG Question 2: Which of the following is the platinum-based chemotherapeutic agent used as first-line treatment for ovarian carcinoma?

• A. Cyclophosphamide
• B. Methotrexate
• C. Cisplatin (Correct Answer)
• D. Dacarbazine

Molecular Biology and Genomics Explanation: ***Cisplatin*** - **Cisplatin** is a platinum-based chemotherapy drug that forms **DNA cross-links**, inhibiting DNA synthesis and leading to the death of rapidly dividing cells, making it highly effective against **ovarian carcinoma**. - It is a cornerstone of chemotherapy regimens for ovarian cancer, often used in combination with other agents such as paclitaxel. *Methotrexate* - **Methotrexate** is an **antimetabolite** that inhibits dihydrofolate reductase, thereby interfering with DNA synthesis. - While it is used in various cancers like leukemia, lymphoma, and some solid tumors (e.g., breast cancer, gestational trophoblastic disease), it is **not a primary recommended drug for ovarian carcinoma**. *Cyclophosphamide* - **Cyclophosphamide** is an **alkylating agent** that causes DNA damage, leading to cell death. - It is used in many cancers, including lymphoma, breast cancer, and some leukemias, but it is **not a first-line or primary agent for ovarian carcinoma** in contemporary treatment guidelines. *Dacarbazine* - **Dacarbazine** is an **alkylating agent** primarily used in the treatment of **malignant melanoma** and Hodgkin lymphoma. - It is **not indicated for the treatment of ovarian carcinoma**.

Molecular Biology and Genomics Indian Medical PG Question 3: Which of the following is used to detect abnormal gene sequences EXCEPT?

• A. RFLP analysis
• B. Pyrosequencing
• C. Flow cytometry (Correct Answer)
• D. FISH

Molecular Biology and Genomics Explanation: ***Flow cytometry*** - **Flow cytometry** is primarily used to analyze **cell populations** based on their physical and biochemical characteristics (e.g., size, granularity, and protein expression) by passing them single file through a laser beam, not for direct gene sequencing. - It detects and quantifies cells labeled with **fluorescent antibodies**, making it useful for immunophenotyping, cell sorting, and DNA content analysis, but not for identifying specific gene sequences or mutations. *RFLP analysis* - **Restriction fragment length polymorphism (RFLP) analysis** detects variations in **DNA sequences** by using **restriction enzymes** to cut DNA at specific sites. - Differences in fragment lengths indicate **polymorphisms** or **mutations** within the recognition sites, thereby identifying abnormal gene sequences. *Pyrosequencing* - **Pyrosequencing** is a method of **DNA sequencing** that determines the sequence of nucleotides by detecting the release of pyrophosphate during DNA synthesis. - It is used to identify **single nucleotide polymorphisms (SNPs)** and **short genetic variations**, making it suitable for detecting abnormal gene sequences. *FISH* - **Fluorescence in situ hybridization (FISH)** uses **fluorescently labeled DNA probes** that bind to specific complementary **DNA sequences** on chromosomes. - It is a powerful cytogenetic technique for detecting **chromosomal abnormalities**, such as deletions, translocations, and amplifications, thereby identifying abnormal gene sequences.

Molecular Biology and Genomics Indian Medical PG Question 4: Which of the following is not a tumor suppressor gene?

• A. p53
• B. HER2 (Correct Answer)
• C. RB
• D. BRCA1

Molecular Biology and Genomics Explanation: ***HER2*** - **HER2** (**Human Epidermal growth factor Receptor 2**) is an **oncogene**, meaning it promotes cell growth and division when overexpressed [1]. - It is a **receptor tyrosine kinase** that, when activated, signals cells to grow and divide, and its amplification is associated with aggressive forms of breast cancer [1]. *p53* - **p53** is a well-known **tumor suppressor gene** that plays a critical role in cell cycle control and apoptosis. - It detects DNA damage and can halt cell division or initiate programmed cell death to prevent the proliferation of damaged cells. *BRCA1* - **BRCA1** (**BReast CAncer gene 1**) is a **tumor suppressor gene** involved in DNA repair. - Mutations in BRCA1 are strongly associated with increased risk of hereditary breast and ovarian cancers due to compromised DNA damage repair mechanisms. *RB* - The **retinoblastoma protein (RB)** is a classic example of a **tumor suppressor gene**. - It acts as a gatekeeper for cell cycle progression from G1 to S phase, preventing uncontrolled cell division by binding to and inactivating E2F transcription factors. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 291-294.

Molecular Biology and Genomics Indian Medical PG Question 5: What is the gene fusion associated with Ewing's sarcoma?

• A. EWS-FLI1 (Correct Answer)
• B. FUS-CHOP
• C. EWS-ATF1
• D. PAX3-FOXO1

Molecular Biology and Genomics Explanation: ***EWS-FLI1*** * This is the **most common and characteristic gene fusion** found in Ewing's sarcoma, occurring in about 85% of cases. * The fusion involves the **Ewing sarcoma RNA-binding protein 1 (EWSR1)** gene on chromosome 22 and the **Friend leukemia integration 1 transcription factor (FLI1)** gene on chromosome 11. *PAX3* * **PAX3** gene fusions, particularly **PAX3-FOXO1**, are associated with **alveolar rhabdomyosarcoma**, a different type of soft tissue sarcoma. * While both are pediatric tumors, their genetic drivers and typical histologies differ significantly from Ewing's sarcoma. *FUS-CHOP* * The **FUS-CHOP (DDIT3)** gene fusion is characteristic of **myxoid liposarcoma**, a distinct type of adipocytic tumor. * This fusion involves the **FUS RNA binding protein (FUS)** gene and the **DNA damage inducible transcript 3 (DDIT3)** gene. *EWS-ATF1* * The **EWS-ATF1** gene fusion is a molecular hallmark of **clear cell sarcoma** (also known as malignant melanoma of soft parts). * This fusion involves the **EWSR1** gene and the **activating transcription factor 1 (ATF1)** gene, leading to distinct biological and clinical features compared to Ewing's sarcoma.

Molecular Biology and Genomics Flashcard 1 of 5

Question: In Homologous Recombination, dsDNA breaks are recognized by the _____ protein and the FA Core Complex, which activate BRCA1/2 to recruit enzymes to repair the break

Answer: ATM

Molecular Biology and Genomics Flashcard 2 of 5

Question: Which transcriptional factors are important for cardiac hypertrophy?_____

Answer: GATA4, NFAT and MEF2

Molecular Biology and Genomics Flashcard 3 of 5

Question: In epigenetics, when a histone is _____, the histone unwinds the DNA to make it available for transcription

Answer: acetylated

Molecular Biology and Genomics Flashcard 4 of 5

Question: A _____ is bacteria with plasmids containing DNA fragments representing the majority of the genetic information from a plant or animal.

Answer: genomic library

Molecular Biology and Genomics Flashcard 5 of 5

Question: First step of initiation of mRNA synthesis involves _____ of the ribosome

Answer: dissociation