DNA repair Practice Questions

Q: A software engineer presents to the OPD with 'complaints of easy fatigability. He reports sitting in front of a computer for 12-14 hours a day consuming junk food, and eating few fruits and vegetables. CBC results show hemoglobin (Hb) concentration of $7 \mathrm{gm} \%$ and MCV of 120 fL . What is the most likely cause of anemia?

Folate deficiency. ***Folate deficiency*** - A **macrocytic anemia** with an **MCV of 120 fL** is characteristic of folate deficiency, as folate is vital for **DNA synthesis** in red blood cell production. - The patient's diet of **junk food** and few fruits/vegetables suggests poor nutritional intake, as folate is abundant in leafy greens and fresh produce. *Cyanocobalamin deficiency* - While also causing **macrocytic anemia** with high MCV, cyanocobalamin (Vitamin B12) deficiency often presents with **neurological symptoms** (e.g., neuropathy, cognitive changes) which are not mentioned. - Dietary sources of B12 are primarily **animal products**, and while junk food is poor, a strict vegetarian/vegan diet is a stronger indicator of B12 deficiency. *Acute blood loss* - Acute blood loss typically causes **normocytic, normochromic anemia**, characterized by a normal MCV in the initial stages. - While severe blood loss can lead to fatigue, the **elevated MCV** of 120 fL makes this diagnosis unlikely unless there's a pre-existing macrocytic condition. *Sideroblastic anemia* - Sideroblastic anemia can be **microcytic, normocytic, or macrocytic**, but it is primarily characterized by the presence of **ring sideroblasts** in the bone marrow and iron overload. - It's often associated with **alcoholism, lead poisoning, or myelodysplastic syndromes**, and the typical features of the patient's diet and MCV do not point towards this condition. *Iron deficiency anemia* - Iron deficiency anemia presents with **microcytic, hypochromic anemia** with a **low MCV** (typically <80 fL), not macrocytic anemia. - While iron deficiency is the most common cause of anemia worldwide and can result from poor diet, the **elevated MCV of 120 fL** clearly excludes this diagnosis.

Q: An investigator isolates bacteria from a patient who presented with dysuria and urinary frequency. These bacteria grow rapidly in pink colonies on MacConkey agar. During replication of these bacteria, the DNA strands are unwound at the origin of replication, forming two Y-shaped replication forks that open in opposite directions. At each replication fork, daughter strands are synthesized from the template strands in a 5′ to 3′ direction. On one strand, the DNA is synthesized continuously; on the other strand, the DNA is synthesized in short segments. The investigator finds that three enzymes are directly involved in elongating the DNA of the lagging strand in these bacteria. One of these enzymes has an additional function that the others do not possess. Which of the following steps in DNA replication is unique to this enzyme?

Excision of nucleotides with 5'→3' exonuclease activity. ***Excision of nucleotides with 5'→3' exonuclease activity*** - **DNA polymerase I** possesses unique **5'→3' exonuclease activity** that allows it to remove RNA primers synthesized by primase. - After primer removal, DNA polymerase I synthesizes DNA in the 5'→3' direction to fill the gap. *Elongation of lagging strand in 5'→3' direction* - While **DNA polymerase I** elongates the lagging strand, this 5'→3' synthesis function is also shared by **DNA polymerase III**, which is the primary enzyme for DNA synthesis. - Therefore, this specific function is not unique to the enzyme in question (DNA polymerase I) as DNA polymerase III also performs 5'→3' elongation. *Prevention of reannealing of the leading strand and the lagging strand* - This function is carried out by **single-strand binding proteins (SSBs)**, which bind to the separated DNA strands to prevent them from reannealing and protect them from degradation. - This is not a function of any DNA polymerase. *Creation of ribonucleotide primers* - The synthesis of short RNA primers required for initiation of DNA synthesis is performed by **primase**, an RNA polymerase. - DNA polymerases do not create primers but rather extend them. *Proofreading for mismatched nucleotides* - **DNA polymerase I** and **DNA polymerase III** both possess **3'→5' exonuclease activity** for proofreading, allowing them to remove incorrectly incorporated nucleotides. - Since this function is shared by DNA polymerase III, it is not unique to DNA polymerase I.

Q: An investigator is studying the replication of bacterial DNA with modified nucleotides. After unwinding, the double-stranded DNA forms a Y-shaped replication fork that separates into two strands. At each of these strands, daughter strands are synthesized. One strand is continuously extended from the template strands in a 5′ to 3′ direction. Which of the following is exclusively associated with the strand being synthesized away from the replication fork?

Repeated activity of ligase. ***Repeated activity of ligase*** - The lagging strand, synthesized away from the replication fork, is made in fragments (**Okazaki fragments**) due to the 5' to 3' synthesis direction of DNA polymerase. - **DNA ligase** repeatedly joins these Okazaki fragments together, forming a continuous strand. *Reverse transcriptase activity* - **Reverse transcriptase** synthesizes DNA from an RNA template, which is not involved in normal bacterial DNA replication. - This enzyme is characteristic of **retroviruses** and certain eukaryotic telomere maintenance. *Elongation in the 3'→5' direction* - DNA polymerases only synthesize new DNA strands in the **5' to 3' direction**. - While reading the template strand in the 3' to 5' direction, the daughter strand is always built from 5' to 3'. *Synthesis of short RNA sequences* - **RNA primers** are synthesized by **primase** on both the leading and lagging strands to initiate DNA synthesis. - This process is not exclusive to the strand synthesized away from the replication fork; the leading strand also requires an initial RNA primer. *5' → 3' exonuclease activity* - The **5' to 3' exonuclease activity** of DNA polymerase I in bacteria is responsible for removing RNA primers. - This activity occurs on both the leading and lagging strands, as both require primer removal.

Q: While performing a Western blot, a graduate student spilled a small amount of the radiolabeled antibody on her left forearm. Although very little harm was done to the skin, the radiation did cause minor damage to the DNA of the exposed skin by severing covalent bonds between the nitrogenous bases and the deoxyribose sugar, leaving several apurinic/apyrimidinic sites. Damaged cells would most likely repair these sites by which of the following mechanisms?

Base excision repair. **Base excision repair** - This mechanism is specifically involved in correcting **single-base DNA damage** or **modified bases**, such as **apurinic/apyrimidinic (AP) sites**. - It involves removing the damaged base by a **DNA glycosylase**, creating an AP site, which is then processed by an **AP endonuclease** to cleave the phosphodiester backbone, followed by DNA polymerase and ligase. *Nucleotide excision repair* - Primarily repairs **bulky DNA lesions**, such as **thymine dimers** caused by UV radiation, or damage from chemical adducts that distort the DNA helix. - It involves excising a larger oligonucleotide containing the damage, not just a single base. *Nonhomologous end joining repair* - This pathway is used to repair **double-strand DNA breaks**, where both strands of the DNA molecule are broken. - It is a "quick-and-dirty" repair mechanism that ligates the broken ends together, often leading to small insertions or deletions. *Homologous recombination* - A repair mechanism for **double-strand DNA breaks** that uses a homologous DNA template (e.g., sister chromatid) to accurately repair the break. - This process is highly accurate but occurs only when a homologous template is available, typically during the S and G2 phases of the cell cycle. *Mismatch repair* - Corrects **base-pair mismatches** and **small insertions/deletions** that occur during DNA replication, which were not corrected by DNA polymerase proofreading. - It targets newly synthesized DNA strands based on methylation patterns in the parental strand.

Q: A 54-year-old woman with breast cancer comes to the physician because of redness and pain in the right breast. She has been undergoing ionizing radiation therapy daily for the past 2 weeks as adjuvant treatment for her breast cancer. Physical examination shows erythema, edema, and superficial desquamation of the skin along the right breast at the site of radiation. Sensation to light touch is intact. Which of the following is the primary mechanism of DNA repair responsible for preventing radiation-induced damage to neighboring neurons?

Nonhomologous end joining repair. ***Nonhomologous end joining repair*** - This pathway is crucial for repairing **double-strand DNA breaks**, which are a major form of damage caused by **ionizing radiation**. - It directly ligates the broken DNA ends without requiring a homologous template, making it an efficient but potentially error-prone repair mechanism. *Homology-directed repair* - This pathway is also used to repair **double-strand DNA breaks** but requires a **homologous DNA template** (usually a sister chromatid) for accurate repair. - While highly accurate, it is typically active during the S and G2 phases of the cell cycle and is generally slower and less dominant than NHEJ for immediate radiation-induced damage in non-dividing cells like neurons. *Base excision repair* - This mechanism primarily corrects damage to individual DNA bases, such as **oxidative damage**, alkylation, or deamination. - It is not the primary mechanism for repairing the **double-strand breaks** induced by ionizing radiation. *DNA mismatch repair* - This pathway corrects errors that arise during **DNA replication**, specifically mismatched base pairs or small insertions/deletions. - It is not involved in repairing radiation-induced DNA damage like **double-strand breaks**. *Nucleotide excision repair* - This pathway repairs bulky DNA lesions, such as those caused by **UV radiation** (e.g., pyrimidine dimers) or chemical mutagens. - It removes a segment of DNA containing the damage but is not the primary repair mechanism for **double-strand breaks** caused by ionizing radiation.

Question 1

A software engineer presents to the OPD with 'complaints of easy fatigability. He reports sitting in front of a computer for 12-14 hours a day consuming junk food, and eating few fruits and vegetables. CBC results show hemoglobin (Hb) concentration of $7 \mathrm{gm} \%$ and MCV of 120 fL . What is the most likely cause of anemia?

Accepted Answer

Folate deficiency

Answer

Cyanocobalamin deficiency

Answer

Acute blood loss

Answer

Sideroblastic anemia

Answer

Iron deficiency anemia

Question 2

An investigator isolates bacteria from a patient who presented with dysuria and urinary frequency. These bacteria grow rapidly in pink colonies on MacConkey agar. During replication of these bacteria, the DNA strands are unwound at the origin of replication, forming two Y-shaped replication forks that open in opposite directions. At each replication fork, daughter strands are synthesized from the template strands in a 5′ to 3′ direction. On one strand, the DNA is synthesized continuously; on the other strand, the DNA is synthesized in short segments. The investigator finds that three enzymes are directly involved in elongating the DNA of the lagging strand in these bacteria. One of these enzymes has an additional function that the others do not possess. Which of the following steps in DNA replication is unique to this enzyme?

Accepted Answer

Excision of nucleotides with 5'→3' exonuclease activity

Answer

Elongation of lagging strand in 5'→3' direction

Answer

Prevention of reannealing of the leading strand and the lagging strand

Answer

Creation of ribonucleotide primers

Answer

Proofreading for mismatched nucleotides

Question 3

An investigator is studying the replication of bacterial DNA with modified nucleotides. After unwinding, the double-stranded DNA forms a Y-shaped replication fork that separates into two strands. At each of these strands, daughter strands are synthesized. One strand is continuously extended from the template strands in a 5′ to 3′ direction. Which of the following is exclusively associated with the strand being synthesized away from the replication fork?

Accepted Answer

Repeated activity of ligase

Answer

Reverse transcriptase activity

Answer

Elongation in the 3'→5' direction

Answer

Synthesis of short RNA sequences

Answer

5' → 3' exonuclease activity

Question 4

While performing a Western blot, a graduate student spilled a small amount of the radiolabeled antibody on her left forearm. Although very little harm was done to the skin, the radiation did cause minor damage to the DNA of the exposed skin by severing covalent bonds between the nitrogenous bases and the deoxyribose sugar, leaving several apurinic/apyrimidinic sites. Damaged cells would most likely repair these sites by which of the following mechanisms?

Accepted Answer

Base excision repair

Answer

Nucleotide excision repair

Answer

Nonhomologous end joining repair

Answer

Homologous recombination

Answer

Mismatch repair

Question 5

A 54-year-old woman with breast cancer comes to the physician because of redness and pain in the right breast. She has been undergoing ionizing radiation therapy daily for the past 2 weeks as adjuvant treatment for her breast cancer. Physical examination shows erythema, edema, and superficial desquamation of the skin along the right breast at the site of radiation. Sensation to light touch is intact. Which of the following is the primary mechanism of DNA repair responsible for preventing radiation-induced damage to neighboring neurons?

Accepted Answer

Nonhomologous end joining repair

Answer

Homology-directed repair

Answer

Base excision repair

Answer

DNA mismatch repair

Answer

Nucleotide excision repair

DNA repair — MCQs

DNA repair — MCQs

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