Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). Patients develop extreme photosensitivity and skin cancers. In NER, which step is specifically defective in the most common XP complementation group (XP-C)?

• A Recognition and binding of bulky DNA distortions in global genome NER ✓
• B Dual incision by XPF-ERCC1 and XPG endonucleases to excise the damaged oligonucleotide
• C Recruitment of RNA Pol II to couple transcription with repair (transcription-coupled NER)
• D DNA synthesis by DNA polymerase delta to fill the excision gap

Explanation

XPC (with hHR23B) is the primary damage-recognition factor for global genome NER (GG-NER). It recognizes and binds to bulky DNA distortions (such as pyrimidine dimers) and recruits the TFIIH complex, which contains XPD and XPB helicases that unwind the DNA. XP complementation group C mutations impair this initial recognition step in GG-NER. Transcription-coupled NER (TC-NER) is affected in XP-B, XP-D, and Cockayne syndrome (CSA, CSB), not XP-C. The incision step involves XPF/ERCC1 and XPG, which are defective in XP-F and XP-G respectively.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.