Question

HNPCC has defect in:

• A. Nucleotide excision
• B. Base pair excision
• C. Point mutation
• D. Mismatch repair gene

Hint:

Recall which DNA repair pathway corrects replication errors and is defective in Lynch syndrome.

Answer 1

The Correct Option is D

Step 1: Define HNPCC. Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also called Lynch Syndrome, is the most common hereditary colorectal cancer syndrome. It is caused by germline mutations in DNA mismatch repair (MMR) genes.

Step 2: Understand the defect. HNPCC is caused by mutations in MMR genes: MSH2, MLH1, MSH6, PMS2, or EPCAM. These genes normally detect and correct base-pair mismatches that occur during DNA replication. When these genes are defective, replication errors accumulate, leading to microsatellite instability (MSI) and ultimately malignant transformation.

Step 3: Distinguish from other repair mechanisms.
- Nucleotide excision repair (NER): Corrects bulky adducts and pyrimidine dimers; defects cause Xeroderma Pigmentosa.
- Base excision repair (BER): Repairs abasic sites and oxidative damage; defects linked to MUTYH-associated polyposis.
- Point mutation: Not a DNA repair mechanism; it is a type of mutation, not the defect classification for HNPCC.

Conclusion: HNPCC is caused by a defect in the mismatch repair (MMR) gene pathway.