Ultraviolet radiation: DNA damage, repair, and human disorders

Ultraviolet (UV) radiation is one of the most common environmental health hazards that cause highly toxic effects in most living organisms. UV irradiation leads to harmful effects including skin aging, eye damage, and skin cancer because of increased production of cellular reactive oxygen species and by direct DNA damage. Damaged DNA, if not properly repaired, is a source of mutation, and interferes with many cellular mechanisms such as replication, transcription, and the cell cycle. Because most UV damaged DNA is efficiently repaired by nucleotide excision repair (NER), which is a specialized UV-induced DNA damage repair system, many UV-induced symptoms are closely related to NER. Therefore, understanding the function of NER genes will elucidate the cause of different UV-induced symptoms. Furthermore, a multidisciplinary understanding of damaged DNA repair systems and other cellular mechanisms affected by unrepaired DNA damage would lead to an improved understanding of UV-induced symptoms and toward developing various preventive and therapeutic methods against UV damage. For this purpose, in this review we discuss two NER-related human genetic disorders, xeroderma pigmentosum (XP) and Cockayne syndrome (CS), the cellular mechanisms that are impaired by defective NER genes, and the functions of RAD2/XPG in relation to the cause of various UV damage-induced symptoms.