The xeroderma pigmentosum C (XPC) protein has a central role in initiating global-genome NER (nucleotide excision repair) by recognising the lesion and recruiting downstream factors. This entry includes the yeast XPC orthologue Rad4 bound to DNA containing a cyclobutane pyrimidine dimer (CPD) lesion. Rad4 inserts a beta-hairpin through the DNA duplex, causing the two damaged base pairs to flip out of the double helix. The expelled nucleotides of the undamaged strand are recognised by Rad4, whereas the two CPD-linked nucleotides become disordered. These findings indicate that the lesions recognised by Rad4/XPC thermodynamically destabilise the Watson-Crick double helix in a manner that facilitates the flipping-out of two base pairs.

This superfamily represents the beta-hairpin domain BHD1 of the Rad4 protein, which is involved in DNA binding.

PFAM:PF10403, INTERPRO:IPR018326,DOI:10.1038/nature06155