Other Proteins Interacting with XP Proteins

Genetic defects in Nucleotide excision repair (NER) lead to the clinical disorder xeroderma pigmentosum (XP) in humans which is characterized by dramatically increased sensitivity to UV light and a predisposition to development of skin cancers.1,2 NER is a major mechanism of DNA repair in cells for the removal of a large variety of bulky DNA lesions induced by environmental genotoxic agents and chemicals. The molecular basis of XP has been attributed to mutations in any of the eight XP genes, XPA through G whose products are required for NER-mediated removal of DNA damage and XP-variant (XPV). The XP proteins involved in NER can be divided into three groups based on their activity in the NER process. XPA, XPC and XPE are required for sensing DNA damage and initiating the repair process. XPB and XPD, components of the basal transcription factor TFIIH, are helicases that create a DNA strand opening surrounding the adducted base(s) during NER. XPG and XPF are the endonucleases that perform the dual incisions to release the damaged strand and allow resynthesis using the nondamaged strand as a template.3-5 Protein-protein interactions are integral for the correct assembly of the pre-incision complex and for the positioning of the nucleases prior to incision. However, these proteins have been found to form complexes with other proteins not directly involved in the NER mechanism. This chapter describes these proteins and their interactions and discusses their effects on the XP proteins, DNA repair, and genome stability