Nucleotide Excision Repair in Eukaryotes

Abstract

Nucleotide excision repair (NER) is the main pathway used by mammals to remove bulky DNA lesions such as those formed by UV light, environmental mutagens, and some cancer chemotherapeutic adducts from DNA. Deficiencies in NER are associated with the extremely skin cancer-prone inherited disorder xeroderma pigmentosum. Although the core NER reaction and the factors that execute it have been known for some years, recent studies have led to a much more detailed understanding of the NER mechanism, how NER operates in the context of chromatin, and how it is connected to other cellular processes such as DNA damage signaling and transcription. This review emphasizes biochemical, structural, cell biological, and genetic studies since 2005 that have shed light on many aspects of the NER pathway. N ucleotide excision repair (NER) is the main pathway responsible for the removal of bulky DNA lesions induced by UV irradiation, environmental mutagens, and certain chemotherapeutic agents. The history of the discovery of NER, its association with genetic disorders, mechanistic features, and relationship with other cellular pathways has been extensively reviewed in 2005 in several articles in DNA Repair and Mutagenesis (Friedberg et al. 2005). Here, I will briefly reiterate how the field of NER developed over the past 50 years and then focus on how our knowledge has progressed since 2005.