Molecular mechanisms of DNA damage recognition and chromatin dynamics regulating mammalian nucleotide excision repair

Nucleotide excision repair (NER) is a principal DNA repair system that can remove a wide variety of DNA lesions caused mainly by environmental agents such as ultraviolet irradiation and chemical compounds. In global genome NER (GG-NER) of higher eukaryotes, initial lesion recognition depends on the specific DNA-binding proteins XPC and UV-DDB. Recent biochemical and structural studies have revealed the sophisticated molecular mechanism of DNA lesion recognition, which accounts for the versatility, efficiency, and accuracy of GG-NER. On the other hand, in living cells, dynamic regulation of higher-order chromatin structures is required to enable lesion recognition and subsequent repair reactions, whereas a comprehensive understanding of the underlying principles and mechanisms remains to be established. In this article, we summarize current knowledge of the mechanism and regulation of DNA lesion recognition in GG-NER, with a particular focus on the functional impacts of chromatin dynamics.