Xeroderma Pigmentosum (XP) Featured Collection

Cells are equipped with multiple DNA repair pathways to deal with the broad spectrum of factors that can cause DNA damage. Nucleotide excision repair (NER) is an essential DNA repair pathway that repairs DNA lesions caused by exposure to UV light. Defects in NER are associated with several genetically inherited disorders including xeroderma pigmentosum (XP). XP is an autosomal recessive disease that is mainly characterized by a susceptibility to UV-induced skin cancer and in some cases neurological abnormalities. Seven XP complementation groups, XPA-XPG, have been identified and represent genes critical to the NER pathway. An additional group, XPV, has been identifi ed in a variant form of XP and represents a gene that encodes a specialized DNA polymerase (PolH) that functions in translesion synthesis. As components of the NER pathway, the XP factors perform various functions required for the elimination of UV-induced lesions. XPE and XPC appear to play a role in DNA damage recognition, while XPB and XPD function as DNA helicases that unwind DNA around lesions. Following unwinding, XPG and XPA function in facilitating the assembly of a pre-incision complex so that the 5’ endonuclease XPF, along with XPG, can excise the damaged bases. There is accumulating evidence that indicates additional functions for XP factors outside of NER. Further studies of these alternate functions will provide new insight into the processes involved in carcinogenesis and cancer risk.