Recognition of Bulky Lesions by Mammalian NER Factors

The NER pathway is also present in prokaryotic organisms, such as Escherichia coli, as well as in eukaryotes from yeast to mammals. Many of the basic steps of NER are evolutionarily conserved, including damage recognition and dual incisions to excise the lesion, helicase activity to displace the excised oligonucleotide and repair factors, and synthesis and ligation enzymes to seal the nick [19, 20], Nevertheless, the biochemical features in prokaryotes and eukaryotes are distinct. 

NER in bacteria involves only three proteins to carry out the complete process of damage recognition and excision UvrA, UvrB, and UvrC. Owing to its relative simplicity, the UvrABC system has been studied extensively, particularly in E. coli, and serves as a model system for NER [20, 21]. 

Bipartite Model of Mammalian NER and the Multipartite Model of Lesion Recognition 

DNA duplex. Naegeli et al. have previously advanced a bipartite model of NER substrate discrimination that is initiated by the detection of disrupted Watson-Crick base-pairing followed by a lesion-sensing step that verifies the presence of a chemically altered nucleotide [29, 33]. The nature of the critically important verification step that leads to the dual incision is still not well understood [24]. The bipartite model is consistent with previous observatisons of Sugasawa et al. who found that XPC/HR23B binds to DNA that contains bubbles of several mismatched DNA bases in the absence of lesions or chemically modified nucleotides, but incisions occur only when a chemically modified base is also present [13, 35]. 

DNA Lesions Derived from the Reactions of PAH Diol Epoxides with DNA are Excellent Substrates for Probing the Mechanisms of NER 

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