DNA repair US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for DNA repair. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
DNA repair US Medical PG Question 1: A 5-month-old male infant from a consanguineous marriage presents with severe sunburns and freckling in sun exposed areas. The mother explains that the infant experiences these sunburns every time the infant goes outside despite applying copious amounts of sunscreen. Which of the following DNA repair mechanisms is defective in this child?
- A. Non-homologous end joining
- B. Homologous recombination
- C. Base excision repair
- D. Mismatch repair
- E. Nucleotide excision repair (Correct Answer)
DNA repair Explanation: ***Nucleotide excision repair***
- The symptoms of **severe sunburns** and **freckling in sun-exposed areas** are classic manifestations of **Xeroderma Pigmentosum (XP)**.
- XP is caused by a defect in **nucleotide excision repair (NER)**, which is crucial for removing **UV-induced DNA damage**, such as **pyrimidine dimers**.
*Non-homologous end joining*
- This mechanism repairs **double-strand DNA breaks** by directly ligating the broken ends, often with some loss of genetic information.
- Defects in non-homologous end joining are associated with conditions like **immunodeficiency** and increased cancer risk, but not with UV sensitivity like XP.
*Homologous recombination*
- This high-fidelity repair pathway uses a **homologous DNA template** to accurately repair **double-strand breaks** and interstrand crosslinks.
- Impaired homologous recombination is linked to conditions like **Fanconi anemia** and increased risk of certain cancers, but not primarily to UV hypersensitivity.
*Base excision repair*
- **Base excision repair (BER)** is responsible for removing **damaged or modified bases** from DNA, such as oxidized or alkylated bases.
- Defects in BER can lead to increased spontaneous mutagenesis and cancer, but do not explain the specific sensitivity to UV light seen in this infant.
*Mismatch repair*
- **Mismatch repair (MMR)** corrects errors that occur during DNA replication, such as **base mismatches** or small insertions/deletions.
- Defective MMR is strongly associated with **hereditary nonpolyposis colorectal cancer (Lynch syndrome)**, but not with severe reactions to sun exposure.
DNA repair US Medical PG Question 2: A 42-year-old woman presents to her primary care physician with fatigue. She reports that over the past 2 months, she has felt increasingly tired despite no changes in her diet or exercise. Her past medical history is notable for obesity, seasonal allergies, and hypertension. She takes ranitidine as needed and hydrochlorothiazide daily. Her family history is notable for colorectal cancer in her mother and maternal uncle, endometrial cancer in her maternal aunt, and ovarian cancer in her maternal grandmother. Her temperature is 98.8°F (37.1°C), blood pressure is 132/71 mmHg, pulse is 89/min, and respirations are 17/min. On exam, she has conjunctival pallor. A stool sample is hemoccult positive. A colonoscopy reveals a fungating hemorrhagic mass in the ascending colon. Which of the following processes is likely impaired in this patient?
- A. Mismatch repair (Correct Answer)
- B. Non-homologous end joining
- C. Homologous recombination
- D. Base excision repair
- E. Nucleotide excision repair
DNA repair Explanation: ***Mismatch repair***
- The patient's presentation with **colorectal cancer** at a relatively young age (42), combined with a strong family history of various cancers (colorectal, endometrial, ovarian) suggesting a **hereditary cancer syndrome**, points towards a defect in **mismatch repair (MMR)**.
- Defective MMR leads to an accumulation of **mutations** during DNA replication, particularly in microsatellites, and is characteristic of **Lynch syndrome** (Hereditary Nonpolyposis Colorectal Cancer, HNPCC).
*Non-homologous end joining*
- This pathway is crucial for repairing **double-strand breaks** in DNA but is often error-prone.
- Defects in non-homologous end joining are associated with conditions like **severe combined immunodeficiency** due to impaired V(D)J recombination, not typically Lynch syndrome.
*Homologous recombination*
- Involved in high-fidelity repair of **double-strand breaks** using a homologous DNA template.
- Impairments are linked to increased risk of certain cancers, such as **BRCA1/2 mutations** causing breast and ovarian cancer, but are not the primary defect in Lynch syndrome.
*Base excision repair*
- This pathway is responsible for repairing **small, non-helix-distorting base lesions** caused by oxidation, alkylation, or deamination.
- Defects can lead to increased mutagenicity but are not the primary mechanism underlying the cancer spectrum seen in Lynch syndrome.
*Nucleotide excision repair*
- This system repairs **bulky DNA adducts** and helix-distorting lesions, such as those caused by UV radiation (e.g., **pyrimidine dimers**).
- Defects are associated with conditions like **xeroderma pigmentosum**, characterized by extreme sun sensitivity and skin cancers, which is not consistent with this patient's presentation.
DNA repair US Medical PG Question 3: A 71-year-old man with colorectal cancer comes to the physician for follow-up examination after undergoing a sigmoid colectomy. The physician recommends adjuvant chemotherapy with an agent that results in single-stranded DNA breaks. This chemotherapeutic agent most likely has an effect on which of the following enzymes?
- A. DNA polymerase III
- B. Topoisomerase I (Correct Answer)
- C. Helicase
- D. Telomerase
- E. Topoisomerase II
DNA repair Explanation: ***Topoisomerase I***
- **Topoisomerase I** creates **single-stranded DNA (ssDNA) breaks** to relieve torsional stress during DNA replication and transcription.
- Many chemotherapeutic agents, such as camptothecin and its derivatives (e.g., irinotecan, topotecan), target topoisomerase I, leading to DNA damage and apoptosis in cancer cells.
*DNA polymerase III*
- **DNA polymerase III** is primarily involved in bacterial DNA replication, synthesizing new DNA strands in a 5' to 3' direction.
- While essential for bacterial survival, it is not the target of chemotherapeutic agents that induce single-stranded DNA breaks in human cells.
*Helicase*
- **Helicase** is responsible for unwinding the DNA double helix during replication and transcription, separating the two strands.
- While its function is critical for DNA processes, it does not directly create DNA breaks as its primary mechanism of action.
*Telomerase*
- **Telomerase** is an enzyme that maintains telomere length at the ends of chromosomes, particularly active in cancer cells.
- Inhibitors of telomerase aim to shorten telomeres, leading to cellular senescence or apoptosis, but they do not primarily cause single-stranded DNA breaks.
*Topoisomerase II*
- **Topoisomerase II** creates **double-stranded DNA (dsDNA) breaks** to untangle and decatenate DNA.
- Though also a target for chemotherapy (e.g., etoposide, doxorubicin), its mechanism involves double-stranded breaks, not single-stranded breaks as specified in the question.
DNA repair US Medical PG Question 4: A 34-year-old woman comes to the physician for evaluation of a breast lump she noticed 2 days ago while showering. She has no history of major illness. Her mother died of ovarian cancer at age 38, and her sister was diagnosed with breast cancer at age 33. Examination shows a 1.5-cm, nontender, mobile mass in the upper outer quadrant of the left breast. Mammography shows pleomorphic calcifications. Biopsy of the mass shows invasive ductal carcinoma. The underlying cause of this patient's condition is most likely a mutation of a gene involved in which of the following cellular events?
- A. Repair of double-stranded DNA breaks (Correct Answer)
- B. Inhibition of programmed cell death
- C. Regulation of intercellular adhesion
- D. Activity of cytoplasmic tyrosine kinase
- E. Arrest of cell cycle in G1 phase
DNA repair Explanation: ***Repair of double-stranded DNA breaks***
- The patient's **family history** (mother with ovarian cancer at 38, sister with breast cancer at 33) and early onset of **invasive ductal carcinoma** strongly suggest an inherited cancer syndrome.
- **BRCA1 and BRCA2 genes** are tumor suppressor genes responsible for repairing **double-stranded DNA breaks**, and mutations in these genes significantly increase the risk of breast and ovarian cancers.
*Inhibition of programmed cell death*
- Mutations leading to the **inhibition of programmed cell death (apoptosis)**, such as those affecting the **Bcl-2 gene**, can contribute to cancer by allowing damaged cells to survive and proliferate.
- While relevant to cancer pathogenesis, it is not the primary mechanism associated with the specific familial breast/ovarian cancer pattern seen here, which points more directly to DNA repair defects.
*Regulation of intercellular adhesion*
- Defects in **intercellular adhesion**, often involving **E-cadherin** (CDH1 gene) mutations, are associated with cancers like **lobular breast carcinoma** and **hereditary diffuse gastric cancer**.
- This patient has **invasive ductal carcinoma**, and the specific familial pattern is less characteristic of intercellular adhesion defects.
*Activity of cytoplasmic tyrosine kinase*
- Abnormal **cytoplasmic tyrosine kinase activity** is implicated in various cancers (e.g., **HER2/neu** amplification in breast cancer, **BCR-ABL** fusion in CML).
- While HER2/neu overexpression is common in breast cancer, it is typically a somatic mutation or amplification, and not the underlying germline defect explaining the strong family history of early-onset breast and ovarian cancer.
*Arrest of cell cycle in G1 phase*
- The **arrest of the cell cycle at the G1 phase** is mainly regulated by **p53** and **Rb tumor suppressor genes**, which prevent uncontrolled cell division.
- While mutations in these genes are crucial in many cancers, the specific familial pattern (breast and ovarian cancer) points more strongly to defects in homologous recombination via BRCA1/2, a different DNA repair pathway.
DNA repair US Medical PG Question 5: A 5-year-old girl is brought to the physician by her mother because of a 1-month history of a painful ulcer on her face. She has developed painful sunburns in the past with minimal UV exposure. Examination of the skin shows a 2-cm ulcerated nodule on the left cheek. There are scaly, hyperpigmented papules and plaques over the skin of the entire body. Ophthalmologic examination shows decreased visual acuity, clouded corneas, and limbal injection. Examination of a biopsy specimen from the facial lesion shows poorly-differentiated squamous cell carcinoma. Impairment of which of the following proteins is the most likely cause of this patient's condition?
- A. Rb nuclear protein
- B. Base-specific glycosylase
- C. Excision endonuclease (Correct Answer)
- D. ATM serine/threonine kinase
- E. DNA helicase
DNA repair Explanation: ***Excision endonuclease***
- This patient's presentation with **painful sunburns**, **early-onset squamous cell carcinoma** on the face, and **ocular abnormalities (clouded corneas, decreased visual acuity)** is highly suggestive of **xeroderma pigmentosum (XP)**.
- XP is an autosomal recessive disorder caused by a defect in **nucleotide excision repair (NER)**, which is responsible for removing DNA damage primarily induced by **UV radiation**. **Excision endonucleases** are key enzymes in the initiation phase of NER, recognizing and excising the damaged DNA segment.
*Rb nuclear protein*
- The **Rb nuclear protein** is a tumor suppressor involved in cell cycle regulation (G1/S checkpoint).
- Impairment of Rb is associated with **retinoblastoma** and several other cancers, but not typically with this specific constellation of light sensitivity, skin cancer, and ocular damage seen in XP.
*Base-specific glycosylase*
- **Base-specific glycosylases** are involved in **base excision repair (BER)**, which primarily corrects small, non-helix-distorting base lesions (e.g., deaminated or alkylated bases).
- While important for DNA repair, defects in BER would not explain the extreme UV sensitivity and subsequent skin cancers characteristic of xeroderma pigmentosum, as these are primarily linked to UV-induced pyrimidine dimers.
*ATM serine/threonine kinase*
- **ATM (ataxia-telangiectasia mutated) kinase** is a critical protein involved in initiating the cellular response to **DNA double-strand breaks**.
- Defects in ATM cause **ataxia-telangiectasia**, characterized by cerebellar ataxia, immunodeficiency, and a predisposition to lymphoid malignancies, but not the specific skin and eye findings of XP.
*DNA helicase*
- **DNA helicases** are enzymes that unwind DNA and are involved in various DNA processes, including replication, recombination, and repair.
- While critical for many functions, a general defect in **DNA helicase** would lead to a broader range of severe developmental and cellular defects, and is not specifically linked to the clinical phenotype of xeroderma pigmentosum which results from specific NER pathway defects.
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