SUMMARY PARAGRAPH for SSL2
In S. cerevisiae, nucleotide excision repair (NER) is mediated by Rad1p, Rad2p, Rad4p, Rad7p, Rad10p, Rad14p, Rad16p, Met18p, the transcription factor TFIIH, 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 7, 8).
The DNA helicases Rad3p and Ssl2p are required for transcription and are involved in the incision step that occurs at the site of damage during NER (9, 10, 11, 12, 13). These diverse roles are carried out by their membership in two complexes: the transcription factor TFIIH and the nucleotide excision factor 3 (NEF3) (14, 15, 5). RAD3 and SSL2 are essential for viability (16, 2). However, a variety of mutations have been made to study the individual contribution of Rad3p and Ssl2p to transcription and NER. A mutation in the nucleotide binding motif of Rad3p does not affect its viability while a similar mutation in Ssl2p is lethal, suggesting the helicase activity of Rad3p is not neccessary for transcription (17, 2). In addition, mutations have been identified in RAD3 and SSL2 that do not affect viability but result in sensitivity (17, 2, 1).
In addition to its role in NER and transcription, Ssl2p has also been implicated in mRNA export from the nucleus (18). Overexpression of Ssl2p confers resistance to the chemotherapeutic drug adriamycin, providing insight into how cancer cells develop resistance to this drug (19, 20).
Ssl2p is related to H. sapiens XPB, also known as ERCC3, which is mutated in patients with xeroderma pigmentosum (XP) and Cockayne's syndrome (2). These disease are collectively known as xeroderma pigmentosum complementation group B. Deletion of the carboxy terminus of S. cerevisiae Ssl2p, which mimics the mutation found in a patient with XP, confers sensitivity to UV (1).
Last updated: 2007-11-07