Cancer susceptibility and DNA repair US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Cancer susceptibility and DNA repair. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Cancer susceptibility and DNA repair US Medical PG Question 1: A 42-year-old woman is seen by her primary care physician for her annual checkup. She has no current concerns and says that she has been healthy over the last year except for a bout of the flu in December. She has no significant past medical history and is not currently taking any medications. She has smoked 1 pack per day since she was 21 and drinks socially with her friends. Her family history is significant for prostate cancer in her dad when he was 51 years of age and ovarian cancer in her paternal aunt when she was 41 years of age. Physical exam reveals a firm, immobile, painless lump in the upper outer quadrant of her left breast as well as 2 smaller nodules in the lower quadrants of her right breast. Biopsy of these lesions shows small, atypical, glandular, duct-like cells with stellate morphology. Which of the following pathways is most likely abnormal in this patient?
- A. Nucleotide excision repair
- B. Base excision repair
- C. Non-homologous end joining
- D. Mismatch repair
- E. Homologous recombination (Correct Answer)
Cancer susceptibility and DNA repair Explanation: ***Homologous recombination***
- The patient's presentation with **multiple, bilateral breast lumps** and a strong family history of **early-onset breast, ovarian, and prostate cancers** suggests a hereditary cancer syndrome, most notably related to **BRCA1/2 mutations**.
- **BRCA1 and BRCA2 genes** are crucial for **homologous recombination**, a major pathway for repairing **double-strand DNA breaks**. Defects in this pathway lead to genomic instability and increased cancer risk.
*Nucleotide excision repair*
- This pathway primarily repairs bulky DNA adducts, such as **pyrimidine dimers** caused by UV radiation, and maintains DNA integrity by excising the damaged segment.
- Deficiencies in nucleotide excision repair are associated with diseases like **xeroderma pigmentosum**, which is characterized by extreme sensitivity to sunlight and skin cancers, not the pattern seen in this patient.
*Base excision repair*
- **Base excision repair** is responsible for repairing small, non-bulky DNA lesions, such as **oxidized or deaminated bases**, by removing the damaged base and replacing it.
- While essential for DNA integrity, its malfunction is not typically linked to the **hereditary breast and ovarian cancer syndrome** suggested by the patient's family history and clinical presentation.
*Non-homologous end joining*
- **Non-homologous end joining (NHEJ)** is an error-prone pathway for repairing **double-strand DNA breaks** by directly ligating the broken ends without a homologous template.
- While critical for DNA repair, defects in NHEJ are not the primary cause of hereditary breast and ovarian cancer, which is more specifically linked to the **BRCA1/2 genes** and the homologous recombination pathway.
*Mismatch repair*
- **Mismatch repair (MMR)** corrects errors that occur during DNA replication, such as mismatched bases or small insertions/deletions.
- Deficiencies in MMR lead to **microsatellite instability** and are characteristic of **Lynch syndrome (hereditary nonpolyposis colorectal cancer)**, which primarily increases the risk of colorectal, endometrial, and other specific cancers, but not the pattern of breast, ovarian, and prostate cancers seen here.
Cancer susceptibility and DNA repair US Medical PG Question 2: A 45-year-old woman presents with heavy menstrual bleeding between her periods. The patient also complains of experiencing an irregular menstrual cycle, weight loss, bloating, and constipation. She has had 3 uncomplicated pregnancies, all of which ended with normal vaginal deliveries at term. She has never taken oral contraception, and she does not take any medication at the time of presentation. She has no family history of any gynecological malignancy; however, her grandfather and mother had colon cancer that was diagnosed before they turned 50. On physical examination, the patient appears pale. Gynecological examination reveals a bloody cervical discharge and slight uterine enlargement. Endometrial biopsy reveals endometrial adenocarcinoma. Colonoscopy reveals several polyps located in the ascending colon, which are shown to be adenocarcinomas on histological evaluation. Which of the following mechanisms of DNA repair is likely to be disrupted in this patient?
- A. Mismatch repair (Correct Answer)
- B. Homologous recombination
- C. Nucleotide-excision repair
- D. Non-homologous end joining
- E. Base-excision repair
Cancer susceptibility and DNA repair Explanation: ***Mismatch repair***
- The patient's presentation with **endometrial adenocarcinoma** and **synchronous colon adenocarcinomas** (diagnosed before age 50 in multiple family members) is highly suggestive of **Lynch syndrome (hereditary nonpolyposis colorectal cancer or HNPCC)**.
- Lynch syndrome is caused by a germline mutation in one of the **DNA mismatch repair (MMR) genes** (e.g., MLH1, MSH2, MSH6, PMS2), leading to an inability to correct replication errors and resulting in microsatellite instability and cancer development.
*Homologous recombination*
- This pathway is crucial for repairing **double-strand DNA breaks** and is often deficient in cancers associated with **BRCA1/2 mutations**, leading to syndromes like hereditary breast and ovarian cancer.
- While homologous recombination defects can cause cancer, they are not typically linked to the specific constellation of endometrial and colon cancers seen in Lynch syndrome.
*Nucleotide-excision repair*
- This pathway is primarily responsible for repairing bulky DNA lesions, such as those caused by **UV radiation** or certain **chemotherapeutic agents**.
- Defects in nucleotide-excision repair are associated with conditions like **xeroderma pigmentosum**, characterized by extreme sensitivity to sunlight and skin cancers, which is not relevant to this patient's presentation.
*Non-homologous end joining*
- This is another major pathway for repairing **double-strand DNA breaks**, but it is generally considered more error-prone than homologous recombination.
- While defects in this pathway can lead to genomic instability and cancer, it is not the primary mechanism disrupted in Lynch syndrome.
*Base-excision repair*
- This pathway is responsible for removing damaged or modified bases from DNA, often initiated by **oxidative damage or alkylation**.
- While essential for maintaining genomic integrity, defects in base-excision repair are not the characteristic mechanism underlying the cancer predisposition seen in Lynch syndrome.
Cancer susceptibility and DNA repair US Medical PG Question 3: A 38-year-old man presents with concerns after finding out that his father was recently diagnosed with colon cancer. Family history is only significant for his paternal grandfather who also had colon cancer. A screening colonoscopy is performed, and a polyp is found in the ascending (proximal) colon, which on biopsy shows adenocarcinoma. A mutation in a gene that is responsible for which of the following cellular functions is the most likely etiology of this patient’s cancer?
- A. DNA mismatch repair (Correct Answer)
- B. Signal transduction
- C. Cytoskeletal stability
- D. Inhibits progression from G1 to S phase
- E. Inhibitor of apoptosis
Cancer susceptibility and DNA repair Explanation: ***DNA mismatch repair***
- The patient's presentation with **early-onset colon cancer** (38 years old), location in the **proximal colon** (ascending colon), and a **strong family history** of colon cancer in his father and paternal grandfather are highly suggestive of **Lynch syndrome (hereditary non-polyposis colorectal cancer or HNPCC)**.
- Lynch syndrome is caused by inherited mutations in **DNA mismatch repair (MMR) genes**, such as *MLH1, MSH2, MSH6*, and *PMS2*, leading to microsatellite instability and an increased risk of various cancers, particularly colorectal and endometrial.
*Signal transduction*
- Mutations in **signal transduction genes (e.g., *KRAS*, *BRAF*)** are common in sporadic colorectal cancer and lead to constitutive activation of cell growth pathways through the RAS/MAPK signaling cascade.
- While mutations in these genes are important in colorectal cancer pathogenesis, they typically do not explain the **familial aggregation, early onset, and proximal location** seen in this patient, which are hallmarks of Lynch syndrome.
*Cytoskeletal stability*
- Genes involved in cytoskeletal stability are crucial for cell structure and migration, but their primary dysfunction is not the direct cause of inherited colorectal cancer syndromes like Lynch syndrome.
- While some advanced cancers may show changes in cytoskeletal proteins, this is not the fundamental genetic defect underlying this specific familial cancer presentation.
*Inhibits progression from G1 to S phase*
- Proteins that inhibit progression from G1 to S phase are typically **tumor suppressor genes**, such as **retinoblastoma protein (Rb)** or **p53**.
- Loss of function in these genes promotes uncontrolled cell division, but mutations in *Rb* or *p53* are not the primary cause of Lynch syndrome; rather, it is characterized by defects in **DNA repair**.
*Inhibitor of apoptosis*
- Genes that inhibit apoptosis (programmed cell death) are often **oncogenes** (e.g., *BCL-2*) or genes that, when mutated, lead to resistance to apoptotic signals.
- While resistance to apoptosis is a hallmark of cancer, the fundamental defect in Lynch syndrome is impaired **DNA repair**, not primarily a direct inhibition of apoptosis.
Cancer susceptibility and DNA repair US Medical PG 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?
- A. Nucleotide excision repair
- B. Nonhomologous end joining repair
- C. Homologous recombination
- D. Mismatch repair
- E. Base excision repair (Correct Answer)
Cancer susceptibility and DNA repair Explanation: **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.
Cancer susceptibility and DNA repair US Medical PG 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?
- A. Homology-directed repair
- B. Base excision repair
- C. Nonhomologous end joining repair (Correct Answer)
- D. DNA mismatch repair
- E. Nucleotide excision repair
Cancer susceptibility and DNA repair Explanation: ***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.
Cancer susceptibility and DNA repair US Medical PG Question 6: 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
Cancer susceptibility and 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.
Cancer susceptibility and DNA repair US Medical PG Question 7: 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
Cancer susceptibility and 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.
Cancer susceptibility and DNA repair US Medical PG Question 8: A 3-year-old male child is found to have a disease involving DNA repair. Specifically, he is found to have a defect in the endonucleases involved in the nucleotide excision repair of pyrimidine dimers. Which of the following is a unique late-stage complication of this child's disease?
- A. Telangiectasia
- B. Colorectal cancer
- C. Malignant melanoma (Correct Answer)
- D. Lymphomas
- E. Endometrial cancer
Cancer susceptibility and DNA repair Explanation: **Malignant melanoma**
- The described condition is **xeroderma pigmentosum**, an autosomal recessive disorder characterized by a defect in **nucleotide excision repair (NER)**, specifically the inability to remove **pyrimidine dimers** caused by **UV radiation**.
- This severely impaired DNA repair leads to an extreme predisposition to **UV-induced skin cancers**, including basal cell carcinomas, squamous cell carcinomas, and, most aggressively, **malignant melanoma**, which is a unique and life-threatening late-stage complication.
*Telangiectasia*
- **Telangiectasias** are dilated small blood vessels that appear on the skin or mucous membranes and can be associated with various conditions.
- While skin abnormalities are prevalent in xeroderma pigmentosum due to sun damage, **melanoma** is a more specific and severe late-stage complication directly resulting from the DNA repair defect.
*Colorectal cancer*
- **Colorectal cancer** is typically associated with other DNA repair defects, such as those in the **mismatch repair system**, as seen in conditions like **Lynch syndrome**.
- It is not a primary or most significant late-stage complication of xeroderma pigmentosum, which is primarily characterized by skin cancers.
*Lymphomas*
- **Lymphomas** are cancers of the lymphatic system, often linked to immune deficiencies or specific genetic translocations.
- While individuals with genetic syndromes can have increased cancer risks, **lymphoma** is not the hallmark late-stage complication of xeroderma pigmentosum; skin cancers are the predominant concern.
*Endometrial cancer*
- **Endometrial cancer** is a gynecological cancer often associated with hormonal factors or genetic predispositions like Lynch syndrome, which involves mismatch repair defects.
- This type of cancer is not a characteristic or unique late-stage complication of xeroderma pigmentosum, whose pathology is centered on **UV-induced DNA damage** and subsequent skin malignancies.
Cancer susceptibility and DNA repair US Medical PG Question 9: A 47-year-old man presents to his primary care physician for fatigue. Over the past 3 months, his tiredness has impacted his ability to work as a corporate lawyer. He denies any changes to his diet, exercise regimen, bowel movements, or urinary frequency. His past medical history is notable for obesity, type II diabetes mellitus, and hypertension. He takes metformin and enalapril. His family history is notable for colorectal cancer in his father and paternal grandfather and endometrial cancer in his paternal aunt. He has a 20-pack-year smoking history and drinks one 6-pack of beer a week. His temperature is 98.8°F (37.1°C), blood pressure is 129/71 mmHg, pulse is 82/min, and respirations are 17/min. On exam, he has conjunctival pallor. A stool sample is positive for occult blood. A colonoscopy reveals a small hemorrhagic mass at the junction of the ascending and transverse colon. Which of the following processes is likely impaired in this patient?
- A. Mismatch repair (Correct Answer)
- B. Homologous recombination
- C. Non-homologous end joining
- D. Nucleotide excision repair
- E. Base excision repair
Cancer susceptibility and DNA repair Explanation: ***Mismatch repair***
- The patient's presentation with **colorectal cancer** at a relatively young age and a strong family history of various cancers (colorectal, endometrial) in **first-degree and second-degree relatives** suggests Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer).
- **Lynch syndrome** is caused by inherited mutations in genes responsible for **DNA mismatch repair**, leading to an accumulation of errors and increased cancer risk.
*Homologous recombination*
- This repair mechanism is crucial for fixing **double-strand DNA breaks** using a homologous DNA template, important for genetic stability and primarily associated with genes like BRCA1/2.
- While defects in homologous recombination can lead to cancer (e.g., **breast and ovarian cancers**), it is not the primary mechanism implicated in Lynch syndrome or the patient's specific presentation of colorectal and endometrial cancer families.
*Non-homologous end joining*
- This is another major pathway for repairing **double-strand DNA breaks**, but it does so by directly ligating the broken ends, often with some loss of genetic information, and does not rely on a homologous template.
- Defects in non-homologous end joining are not typically linked to the specific spectrum of cancers seen in **Lynch syndrome**.
*Nucleotide excision repair*
- This pathway is responsible for removing bulky DNA lesions, such as those caused by **UV light (e.g., pyrimidine dimers)** or certain chemical mutagens, and its defects are associated with conditions like xeroderma pigmentosum.
- The clinical picture and family history are not characteristic of disorders related to impaired **nucleotide excision repair**.
*Base excision repair*
- This repair pathway primarily corrects small, non-bulky DNA lesions, such as **oxidized, alkylated, or deaminated bases**, that do not distort the DNA helix.
- While important for maintaining genomic integrity, defects in base excision repair are typically associated with different cancer susceptibilities and not the specific features of **Lynch syndrome**.
Cancer susceptibility and DNA repair US Medical PG Question 10: An investigator studying DNA mutation mechanisms isolates single-stranded DNA from a recombinant bacteriophage and sequences it. The investigator then mixes it with a buffer solution and incubates the resulting mixture at 70°C for 16 hours. Subsequent DNA resequencing shows that 3.7 per 1,000 cytosine residues have mutated to uracil. Which of the following best describes the role of the enzyme that is responsible for the initial step in repairing these types of mutations in living cells?
- A. Connecting the phosphodiester backbone
- B. Cleavage of the phosphodiester bond 3' of damaged site
- C. Creation of abasic site (Correct Answer)
- D. Release of the damaged nucleotide
- E. Addition of free nucleotides to 3' end
Cancer susceptibility and DNA repair Explanation: ***Creation of abasic site***
- The mutation of **cytosine to uracil** is an example of **deamination**, which is repaired by the **base excision repair (BER)** pathway.
- The initial step in BER involves **DNA glycosylase**, which *removes* the damaged base (uracil) from the sugar-phosphate backbone by hydrolyzing the **N-glycosidic bond**, creating an **abasic site**.
*Connecting the phosphodiester backbone*
- This is the function of **DNA ligase**, which acts at the *final step* of DNA repair pathways to seal the nicks in the backbone.
- It does not initiate the repair process for deaminated bases.
*Cleavage of the phosphodiester bond 3' of damaged site*
- This is typically performed by an **AP endonuclease (APE1)** after the abasic site has been created.
- It is a *subsequent step* in BER, not the initial one for removing the damaged base itself.
*Release of the damaged nucleotide*
- While the damaged base is eventually *released*, the initial enzyme (DNA glycosylase) specifically removes the **base**, leaving the sugar and phosphate intact.
- The entire nucleotide (base, sugar, and phosphate) is typically removed later by an **AP lyase** or APE1, after the initial glycosylase action.
*Addition of free nucleotides to 3' end*
- This is the function of **DNA polymerase**, which fills in the gap after the damaged nucleotide and surrounding region have been excised.
- This occurs *after* the initial recognition and removal of the damaged base, not as the primary repair step.
More Cancer susceptibility and DNA repair US Medical PG questions available in the OnCourse app. Practice MCQs, flashcards, and get detailed explanations.
