Patient with HNPCC (hereditary nonpolyposis colon cancer) has genes with microsatellite instability. This is due to failure of which repair mechanism of DNA
**Core Concept**
Hereditary nonpolyposis colon cancer (HNPCC) is a type of colorectal cancer associated with genetic mutations that lead to microsatellite instability. Microsatellite instability occurs due to defects in the DNA repair machinery, specifically the mismatch repair (MMR) system.
**Why the Correct Answer is Right**
The MMR system corrects errors in DNA replication and recombination by recognizing and repairing mismatched bases. In HNPCC, mutations in genes such as MLH1, MSH2, MSH6, and PMS2 disrupt the MMR system, leading to microsatellite instability and an increased risk of colorectal cancer. This is because the MMR system is essential for maintaining genome stability and preventing the accumulation of mutations.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because the nucleotide excision repair (NER) pathway, which corrects UV-induced DNA damage, is not primarily responsible for microsatellite instability in HNPCC.
**Option B:** This option is incorrect because the base excision repair (BER) pathway, which corrects oxidative damage and aldehydes, is not directly involved in the pathogenesis of HNPCC.
**Option C:** This option is incorrect because the double-strand break repair (DSBR) pathway, which corrects DNA double-strand breaks, is not primarily responsible for microsatellite instability in HNPCC.
**Option D:** This option is incorrect because the homologous recombination repair (HRR) pathway, which corrects DNA double-strand breaks, is not directly involved in the pathogenesis of HNPCC.
**Clinical Pearl / High-Yield Fact**
Molecular testing for MMR deficiency is an important diagnostic tool for HNPCC, and it can guide the use of immunohistochemistry and microsatellite instability testing in the diagnosis of colorectal cancer.
**Correct Answer:** B. Base excision repair is not primarily responsible for microsatellite instability in HNPCC.