XPA gene, its product and biological roles

Abstract

The 31kDa XPA protein is part of the core incision complex of the mammalian nucleotide excision repair (NER) system and interacts with DNA as well as with many other NER subunits. In the absence of XPA, no incision complex can form and no excision of damaged DNA damage occurs. A comparative analysis of the DNA-binding properties in the presence of different substrate conformations indicated that XPA protein interacts preferentially with kinked DNA backbones. The DNA-binding domain of XPA protein displays a positively charged cleft that is involved in an indirect readout mechanism, presumably by detecting the increased negative potential encountered at sharp DNA bends. We propose that this indirect recognition function contributes to damage verification by probing the susceptibility of the DNA substrate to be kinked during the assembly of NER complexes. © 2009 Springer New York.