The XPE protein binds to CPDs and is involved in GGR of CPDs. Patients in the XP-E complementation group have mild dermatological symptoms and no neurological malfunctions. In most cases, cells derived from XP-E individuals have an NER level between 40 and 60% of normal cells and only slight UV sensitivity. The role of XPE in NER remained unclear until recently, as it was not required for in vitro systems that were dependent on all the other known NER proteins.

Band shift assays using UV-irradiated plasmids indicate that in some XP-E cell lines, a damaged DNA-binding protein is absent (35). This DNA damage-binding activity (UV-DDB) has been purified as a protein complex with two subunits of 128 and 48 kD (36). Sequence analysis of the p48 subunit has revealed mutations in the p48 gene in several XP-E patients (37,38), indicating that p48 is the XPE gene. However, other XP-E cell lines show normal levels of DDB activity, and they have no mutations in the p48 or the p127 subunits. It is quite likely that the relatively high levels of NER in these patients has led to incorrect assignment to the XP-E group.

Hwang and coworkers (39) have shown that the p48 XPE gene is UV in-ducible, and that this induction is dependent on p53. Furthermore, they showed that XPE is specifically involved in global genome repair of cyclobutane pyrimi-dine dimmers (CPDs), but it is not required for the removal of 6-4 PPs or for the transcription-coupled repair of CPDs. This accounts for the mild cellular and clinical features of XP-E patients.

Recent data indicate that DDB also has a possible transcription-stimulatory activity (40,41), and that it could function as a transcriptional partner of E2F1. Datta et al. (42) have shown that the p48 subunit of DDB (damaged DNA binding) protein associates with the CBP/p300 family of histone acetyltransferase in vivo and in vitro, implying a possible involvement of DDB in chromatin remodeling for recruitment of the NER machinery at the injured sites.

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