SUMMARY PARAGRAPH for RAD14
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, 3).
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 (4). In NEF1, Rad14p and Rad10p form tight interactions with Rad1p but not with each other (4, 5). NEF1 targeting is mediated by Rad14p, which recognizes and binds the damaged DNA (6). 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 (7, 8). The Rad1p/Rad10p endonuclease is structure-specific and cleaves 3'-ended single stranded DNA at its junction with the duplex DNA (8).
Rad14p is a zinc metalloprotein and mutations in rad14 result in UV sensitivity (9, 10). RAD14 is the functional homolog of the human gene XPA with the two proteins sharing 54% amino acid similarity (10). Mutations in XPA lead to a frequently occurring and severe form of the disorder xeroderma pigmentosum (XP complementation group A; OMIM); clinical symptoms include neurological abnormalities and increased incidence of skin cancer (10).
Last updated: 2006-03-14