SUMMARY PARAGRAPH for RAD1
In S. cerevisiae, nucleotide excision repair (NER) is mediated by Rad1p, Rad2p, Rad4p, Rad7p, Rad10p, Rad14p, Rad16p, Met18p, the transcription factor TFIIH (composed of Rad3p, Ssl1p, Ssl2p, Tfb1p, Tfb2p, Tfb3p), and the heterotrimeric complex RPA (Rfa1p, Rfa2p, Rfa3p). Together these proteins bind DNA lesions, including UV-induced photoproducts and chemical crosslinks, unwind the surrounding duplex, and make incisions on both sides of the damaged DNA, which releases a fragment of 25-30bp (reviewed in 1, 4).
The various NER proteins assemble into four complexes, NEF1-4 (nucleotide excision repair factors; reviewed in 1). Rad14p, Rad1p, and Rad10p form the complex NEF1 (5). In NEF1, Rad14p and Rad10p form tight interactions with Rad1p but not with each other (5, 6). NEF1 targeting is mediated by Rad14p, which recognizes and binds the damaged DNA (7). Together, Rad1p and Rad10p form a single-strand DNA endonuclease that binds DNA and then nicks the damaged DNA strand on the 5' side of the lesion (8, 9). The Rad1p/Rad10p endonuclease is structure-specific and cleaves 3'-ended single stranded DNA at its junction with the duplex DNA (9).
In addition to their requirement in NER, the RAD1 and RAD10 genes function in mitotic recombination, double-strand break repair via the single-strand annealing pathway, and processing meiotic recombination intermediates (10, 11, 12, 13, 14). RAD1 and RAD10 null mutants are viable but are defective in the preceding processes and show increased sensitivity to UV radiation (15, 16, 10, 14, 13).
RAD1 orthologs have been identified in S. pombe, Arabidopsis, Drosophila, and humans (17, 18, 19, 20). Inactivation of the human homolog, XPF/ERCC4 (OMIM), leads to the disorder xeroderma pigmentosum (XP; OMIM), which is characterized by UV light sensitivity and increased incidence of skin cancer (20).
Last updated: 2006-03-14