Nucleotide excision repair (NER) corrects bulky helix-distorting lesions such as pyrimidine dimers. In global genome NER, which protein complex first recognises the lesion, and what is the significance of XPC mutations?

• A XPA protein first recognises the lesion; XPA mutations cause mild Cockayne syndrome
• B PCNA ring first recognises the lesion; PCNA mutations cause Fanconi anemia
• C XPC-RAD23B complex recognises the lesion; XPC mutations cause xeroderma pigmentosum group C with high risk of skin cancer but no neurological defects ✓
• D MSH2-MSH6 heterodimer first recognises the lesion; its mutation causes xeroderma pigmentosum

Explanation

In global genome NER (GG-NER), the XPC-RAD23B complex performs the initial lesion recognition by detecting helix distortion rather than the lesion chemistry itself. XPA is a scaffolding protein involved in later verification steps. XPC mutations cause XP-C, characterised by early-onset skin cancers on sun-exposed areas but lacking the progressive neurodegeneration seen in XP-A or XP-D (which involve transcription-coupled NER as well). MSH2-MSH6 belongs to mismatch repair, not NER; PCNA is a clamp protein in replication and repair but is not the initial sensor.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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