Project: Xeroderma pigmentosum (XP) patients cannot be exposed to the sunlight since they have a deficient nucleotide excision repair (NER). NER removes mainly lesions caused by UV light. There are more than 30 proteins involved in NER and they are sequentially recruited to sites of damage through protein-protein interactions. One very important interaction is between the XPA and ERCC1 proteins. XPA recruits the heterodimeric endonuclease ERCC1-XPF to NER complexes to carry out the incision 5' to the damage. Abolishment of this association between ERCC1 and XPA results in NER deficiency. So far very vague information was available about the interaction domains of the two proteins. Based on new structural and biochemical data we could identify the residues in both ERCC1 and XPA that are critical for the interaction. Both ERCC1 and XPA mutants show decreased in vitro NER activity. My goal now is to get an in vivo confirmation of the in vitro results.