Fig. 7. Model for the effects of the defect in XP–D/CS cells. (A) In normal cells (I), transcription initiation utilizes TFIIH in its transcription mode (depicted as an ellipse). A signal from a DNA damaged site recruits TFIIH and converts it into repair mode (depicted as a hexagon) (II) and NER takes place. After incision, TFIIH reverts to its transcriptional configuration (III). (B) In XP–D/CS cells, the signal from the damaged site converts TFIIH into its repair conformation (II), but is unable to recruit it to the site of the damage. Nicks are therefore generated at sites of transcription initiation, instead of at repair sites (III).