DNA repair

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.

DNA repair US Medical PG Question 6: A 19-year-old woman presents to the physician for a routine health maintenance examination. She has a past medical history of gastroesophageal reflux disease. She recently moved to a new city to begin her undergraduate studies. Her father was diagnosed with colon cancer at age 46. Her father's brother died because of small bowel cancer. Her paternal grandfather died because of stomach cancer. She takes a vitamin supplement. Current medications include esomeprazole and a multivitamin. She smoked 1 pack of cigarettes daily for 3 years but quit 2 years ago. She drinks 1–2 alcoholic beverages on the weekends. She appears healthy. Vital signs are within normal limits. Physical examination shows no abnormalities. Colonoscopy is unremarkable. Germline testing via DNA sequencing in this patient shows mutations in DNA repair genes MLH1 and MSH2. Which of the following will this patient most likely require at some point in her life?

• A. Celecoxib or sulindac therapy
• B. Surgical removal of a desmoid tumor
• C. Prophylactic proctocolectomy with ileoanal anastomosis
• D. Annual colonoscopy beginning at 20–25 years of age (Correct Answer)
• E. Measurement of carcinoembryonic antigen and CA 19-9 yearly

DNA repair Explanation: ***Annual colonoscopy beginning at 20–25 years of age*** - This patient's family history of multiple cancers at young ages (father with colon cancer at 46, uncle with small bowel cancer, grandfather with stomach cancer) combined with **germline mutations in MLH1 and MSH2** is highly indicative of **Lynch syndrome (hereditary non-polyposis colorectal cancer - HNPCC)**. - Individuals with Lynch syndrome have a significantly increased risk of colorectal cancer, and screening with **annual colonoscopies starting at a young age (20-25 years or 2-5 years younger than the earliest age of diagnosis in the family)** is crucial for early detection and prevention. *Celecoxib or sulindac therapy* - **NSAID therapy** (like celecoxib or sulindac) is sometimes used for **chemoprevention in familial adenomatous polyposis (FAP)** to reduce polyp burden, especially in attenuated FAP. - However, this patient's presentation and genetic findings point to **Lynch syndrome**, for which NSAID chemoprevention is not the primary or most effective strategy compared to surveillance. *Surgical removal of a desmoid tumor* - **Desmoid tumors** are benign but locally aggressive soft tissue tumors that are a characteristic **extracolonic manifestation of familial adenomatous polyposis (FAP)**, especially in patients with mutations in the APC gene. - This patient has **Lynch syndrome**, which is associated with different extracolonic cancers (e.g., endometrial, ovarian, gastric, small bowel), but **desmoid tumors are not a typical feature of Lynch syndrome**. *Prophylactic proctocolectomy with ileoanal anastomosis* - **Prophylactic proctocolectomy** is the standard preventive surgery for individuals with **familial adenomatous polyposis (FAP)** to prevent the inevitable development of colorectal cancer due to hundreds to thousands of polyps. - While Lynch syndrome carries a high risk of colorectal cancer, prophylactic colectomy is generally **not recommended as the initial management** given that surveillance via colonoscopy allows for removal of precancerous polyps and early-stage cancers, reserving surgery for when clinically indicated. *Measurement of carcinoembryonic antigen and CA 19-9 yearly* - **Carcinoembryonic antigen (CEA) and CA 19-9** are **tumor markers** that can be elevated in certain cancers (e.g., colorectal for CEA, pancreatic/biliary for CA 19-9). - However, these markers have **poor sensitivity and specificity for screening healthy, asymptomatic individuals** at high risk for cancer and are primarily used for monitoring disease recurrence or treatment response in diagnosed cancers. They are not recommended for routine surveillance in Lynch syndrome.

DNA repair US Medical PG Question 7: A 7-month-old boy presents to the family physician with extensive scaliness and pigmentation of sun-exposed skin areas. His mother says that these symptoms were absent until mid-spring and then became significantly worse after their trip to California in the summer. The child was born in December to a consanguineous couple after an uncomplicated pregnancy. He is breastfed and receives mashed potatoes, bananas, and carrots as complementary foods. His weight is 8.5 kg (18.7 lb) and length is 70 cm (2 ft 96 in). The patient’s vital signs are within normal limits for his age. On physical examination, there is freckling, scaling, and erythema on the sunlight-exposed areas of the face, trunk, and upper and lower extremities. No blistering, scarring, hypertrichosis, or alopecia is noted. The rest of the exam is unremarkable. Which process is most likely disrupted in this patient?

• A. Nucleotide-excision DNA repair (Correct Answer)
• B. Base-excision DNA repair
• C. Hydroxylation of proline and lysine in the procollagen molecule
• D. Conversion of uroporphyrinogen III to coproporphyrinogen III
• E. NAD production

DNA repair Explanation: ***Nucleotide-excision DNA repair*** - The patient's symptoms (extensive scaliness, pigmentation, freckling, scaling, and erythema on sun-exposed areas) that worsen with sun exposure are characteristic of **xeroderma pigmentosum**. - This condition is caused by a defect in **nucleotide-excision repair (NER)**, which is essential for repairing DNA damage, particularly from UV radiation. *Base-excision DNA repair* - **Base-excision repair (BER)** primarily addresses single-base damage, like oxidized or alkylated bases, not the bulky adducts formed by UV light. - Defects in BER are associated with conditions like colorectal cancer, but not the specific photosensitivity seen here. *Hydroxylation of proline and lysine in the procollagen molecule* - This process is essential for proper collagen synthesis; defects lead to disorders like **Ehlers-Danlos syndrome** or **scurvy**. - These conditions manifest with skin fragility, bruising, and joint hypermobility, not the prominent photosensitivity observed. *Conversion of uroporphyrinogen III to coproporphyrinogen III* - This step is involved in **heme synthesis**; defects can lead to **porphyrias**, which often cause photosensitivity and blistering. - However, the patient's presentation of scaling, freckling, and erythema without blistering or scarring is less typical for porphyria. *NAD production* - **NAD (nicotinamide adenine dinucleotide)** is a crucial coenzyme in many metabolic pathways; its deficiency can lead to pellagra-like symptoms (dermatitis, diarrhea, dementia). - While pellagra can involve sun-exposed skin, it typically involves a more diffuse, symmetrically inflamed rash with hyperpigmentation and thickening, rather than the discrete freckling and scaling described.

DNA repair US Medical PG Question 8: As part of a clinical research study, the characteristics of neoplastic and normal cells are being analyzed in culture. It is observed that neoplastic cell division is aided by an enzyme which repairs progressive chromosomal shortening, which is not the case in normal cells. Due to the lack of chromosomal shortening, these neoplastic cells divide more rapidly than the normal cells. Which of the following enzymes is most likely involved?

• A. Topoisomerase
• B. DNA polymerase
• C. Reverse transcriptase
• D. Protein kinase
• E. Telomerase (Correct Answer)

DNA repair Explanation: ***Telomerase*** - **Telomerase** is an enzyme that adds repetitive nucleotide sequences (telomeres) to the ends of chromosomes, counteracting their progressive shortening during DNA replication. This activity is crucial for the continuous division of neoplastic cells. - In normal somatic cells, **telomerase activity is typically low or absent**, leading to telomere shortening with each division, eventually triggering cellular senescence or apoptosis. The presence of telomerase in neoplastic cells allows them to bypass these natural limits on proliferation. *Topoisomerase* - **Topoisomerases** are enzymes that regulate the supercoiling of DNA by breaking and rejoining DNA strands, which is essential during replication and transcription to relieve torsional stress. - They do not directly repair chromosomal shortening but rather manage the topological state of DNA. *DNA polymerase* - **DNA polymerase** is primarily responsible for synthesizing new DNA strands by adding nucleotides, thereby elongating the DNA molecule during replication and DNA repair processes. - While essential for DNA replication, it cannot fully replicate the very ends of linear chromosomes, leading to the **end-replication problem** and telomere shortening. *Reverse transcriptase* - **Reverse transcriptase** is an enzyme that synthesizes DNA from an RNA template, a process central to retroviruses and some eukaryotic elements like retrotransposons. - Although telomerase itself is a specialized reverse transcriptase (using an RNA template to synthesize DNA telomeres), the general term "reverse transcriptase" does not specifically refer to the enzyme that repairs chromosomal shortening in the context of cell division. *Protein kinase* - **Protein kinases** are enzymes that add phosphate groups to proteins, a process known as phosphorylation. This modification can alter protein activity, localization, or stability, playing a critical role in signal transduction pathways. - They are involved in regulating various cellular processes, including cell growth and division, but do not directly repair chromosomal shortening.

DNA repair US Medical PG Question 9: A 28-year-old woman, gravida 1, para 0, at 20 weeks' gestation comes to the physician for genetic counseling. Her brother and maternal uncle both have anemia that worsens after taking certain medications. Based on the pedigree shown, what is the probability that her son will be affected by the disease?

• A. 12.5%
• B. 100%
• C. 50%
• D. 0%
• E. 25% (Correct Answer)

DNA repair Explanation: ***25%*** - This is an **X-linked recessive** disorder, as evidenced by affected males born to unaffected parents, and the skipping of generations in females. The woman (III-2) is the daughter of a carrier mother (II-1) and an unaffected father (II-2), making her a **carrier** with a 50% probability (X^AX^a). - Since her mother (II-1) is a carrier (as her brother IV-1 is affected and her parents (I-1 and I-2) are unaffected), and her father (II-2) is unaffected, the woman (III-2) has a 50% chance of being a **carrier**. If she is a carrier (X^AX^a) and her son inherits her affected X chromosome, he will be affected. The probability of her son being affected is (0.5 probability of her being a carrier) * (0.5 probability of passing on the affected X to her son) = **0.25 or 25%**. *12.5%* - This value would arise from an incorrect calculation of the woman's carrier status, or the inheritance pattern. - It does not account for the direct inheritance from a carrier mother to a son in an X-linked recessive pattern. *100%* - This would only be possible if the mother was affected (which she is not, as she is female and not shaded) and passing on the affected X to all sons, or if the father was affected in a condition with male-to-male transmission. - The woman (III-2) herself is not affected, indicating she is at most a carrier, not homozygous for the affected allele, nor is the disorder dominant. *50%* - This would be the probability of the son being affected *if* the woman (III-2) was a confirmed carrier, or if the disorder was autosomal dominant if she was affected. - This option incorrectly assumes that the woman (III-2) is a *confirmed* carrier, ignoring the 50% probability that she might not have inherited the carrier status from her mother. *0%* - If the woman (III-2) were not a carrier, or if the disease was autosomal recessive and her partner was unaffected and not a carrier, then the probability would be 0%. - Given the pattern of inheritance and her family history (affected brother and maternal uncle), there is a definite risk of her being a carrier and passing it on.

DNA repair US Medical PG Question 10: An 11-year-old boy is brought to the emergency room with acute abdominal pain and hematuria. Past medical history is significant for malaria. On physical examination, he has jaundice and a generalized pallor. His hemoglobin is 5 g/dL, and his peripheral blood smear reveals fragmented RBC, microspherocytes, and eccentrocytes (bite cells). Which of the following reactions catalyzed by the enzyme is most likely deficient in this patient?

• A. Glucose-1-phosphate + UTP → UDP-glucose + pyrophosphate
• B. Glucose + ATP → Glucose-6-phosphate + ADP + H+
• C. D-glucose 6-phosphate → D-fructose-6-phosphate
• D. Glucose-6-phosphate + H2O → glucose + Pi
• E. D-glucose-6-phosphate + NADP+ → 6-phospho-D-glucono-1,5-lactone + NADPH + H+ (Correct Answer)

DNA repair Explanation: ***D-glucose-6-phosphate + NADP+ → 6-phospho-D-glucono-1,5-lactone + NADPH + H+*** - This reaction is catalyzed by **glucose-6-phosphate dehydrogenase (G6PD)**, an enzyme critical for the production of **NADPH** in the **pentose phosphate pathway**. - **NADPH** is essential for reducing **oxidative stress** in red blood cells. A deficiency in G6PD leads to increased susceptibility to hemolysis, especially under oxidative triggers like malaria, resulting in symptoms such as **acute hemolytic anemia**, jaundice, and specific morphological changes (e.g., **fragmented RBCs**, **microspherocytes**, and **eccentrocytes**, also known as **bite cells**). *Glucose-1-phosphate + UTP → UDP-glucose + pyrophosphate* - This reaction is catalyzed by **UDP-glucose pyrophosphorylase** and is important for **glycogen synthesis**. - A deficiency in this enzyme would primarily affect glycogen metabolism and would not explain the **hemolytic anemia** or the characteristic red blood cell morphology seen in the patient. *Glucose + ATP → Glucose-6-phosphate + ADP + H+* - This reaction is catalyzed by **hexokinase**, the first committed step in **glycolysis**. - While hexokinase deficiency can cause **hemolytic anemia**, it generally presents with chronic, moderate anemia and does not typically involve the specific red blood cell morphology (eccentrocytes/bite cells) associated with oxidative damage found in G6PD deficiency. *D-glucose 6-phosphate → D-fructose-6-phosphate* - This reaction is catalyzed by **phosphoglucose isomerase** (also known as phosphohexose isomerase) and is part of **glycolysis**. - A deficiency in this enzyme would impair glycolysis and lead to **hemolytic anemia**, but its clinical presentation and RBC morphology differ from what is typically seen in G6PD deficiency, particularly the absence of oxidative stress markers like bite cells. *Glucose-6-phosphate + H2O → glucose + Pi* - This reaction is catalyzed by **glucose-6-phosphatase**, an enzyme found primarily in the liver and kidney, responsible for the final step in **gluconeogenesis** and glycogenolysis to release free glucose into the bloodstream. - A deficiency in glucose-6-phosphatase leads to **glycogen storage disease type I (Von Gierke's disease)**, characterized by **hypoglycemia**, **lactic acidosis**, and hepatomegaly, not hemolytic anemia.

DNA repair Flashcard 1 of 10

Question: Which enzyme catalyzes the formation of a phosphodiester bond between Okazaki fragments?_____

Answer: DNA ligase

DNA repair Flashcard 2 of 10

Question: Xeroderma Pigmentosum is an inherited pathology due to a defective _____ pathway

Answer: Nucleotide Excision Repair

DNA repair Flashcard 3 of 10

Question: When using CRISPR/Cas9 that introduce a double strand break to knock-out target DNA, _____ repair the gap introduced by this Cas9 variant

Answer: nonhomologous end joining enzymes

DNA repair Flashcard 4 of 10

Question: What form of DNA repair fixes mutations due to DNA replication errors?_____

Answer: mismatch repair

DNA repair Flashcard 5 of 10

Question: Which base excision repair enzyme is responsible for removing nucleotides at the 5' end?_____

Answer: AP-endonuclease

DNA repair Flashcard 6 of 10

Question: What are the four mechanisms of DNA repair?

Answer: Nuceotide excision repair Base excision repair Mismatch repair Nonhomologous end joining

DNA repair Flashcard 7 of 10

Question: non-homologous end joining

Answer: join 2 dsDNA ends

Extra Information: double-stranded breaks (when no homologous chromosome is around to use as a guide)ataxia telangiectasia

DNA repair Flashcard 8 of 10

Question: mismatch repair

Answer: 1. new strand recognized (lacks methylation) 2. mismatched nucleotides removed 3. DNA pol/ligase fills/seals gap

Extra Information: Mismatched bases on newly synthesized DNA strandhereditary nonpolyposis colorectal cancer (HNPCC)

DNA repair Flashcard 9 of 10

Question: base excision repair (BER)

Answer: 1. specific glycosylases recognize and remove damaged bases 2. AP endonuclease removes AP DNA 3. DNA pol/ligase fill/seal gap

Extra Information: spontaneous/toxic changes to the base itself; most often deamination

DNA repair Flashcard 10 of 10

Question: nucleotide excision repair (NER)

Answer: 1. endonuclease removes short ssDNA segment containing lesion 2. DNA pol/ligase fill/seal gap

Extra Information: bulky adducts, commonly thymine dimers caused by UV radiation xeroderma pigmentosa