Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). Which of the following correctly describes the step in NER that is specifically defective in XPC-deficient patients?

• A XPC is part of the incision machinery that cuts the damaged strand 5' and 3' to the lesion; its deficiency prevents excision of the 24–32 nucleotide oligomer
• B XPC deficiency impairs transcription-coupled NER only; global genome NER remains intact as the damage is recognised by RPA instead
• C XPC deficiency impairs the global genome NER (GG-NER) subpathway by failing to recognise helix-distorting bulky lesions (e.g., CPDs, 6-4 PPs) throughout the genome, while transcription-coupled NER (TC-NER) remains intact ✓
• D XPC deficiency causes failure to verify the correctness of the repair patch by mismatch repair, leading to mutation fixation

Explanation

NER has two subpathways: global genome NER (GG-NER) and transcription-coupled NER (TC-NER). XPC (in complex with HR23B) is the primary damage recognition factor in GG-NER, detecting helix-distorting lesions such as cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts throughout non-transcribed genomic DNA. TC-NER is initiated differently by stalled RNA polymerase II (recognised by CSA/CSB proteins) and does not require XPC. Therefore, XPC-deficient patients have defective GG-NER but intact TC-NER. This is why XP complementation groups (XPA-XPG) have differing clinical severity based on which subpathway is affected.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.