DNA repair deficiencies associated with mutations in genes encoding subunits of transcription initiation factor TFIIH...

Several proteins, including Rad3 and Rad25(Ssl2), are essential for nucleotide excision repair (NER) and function in the RNA polymerase II transcription initiation complex TFIIH. Mutations in genes encoding two other subunits of TFIIH, TFB1 and SSL1, result in UV sensitivity and have been shown to take part in NER in an in vitro system. However, a deficiency in global NER does not exclude the possibility that such repair-deficient mutants can perform transcription-coupled repair (TCR), as shown for xeroderma pigmentosum group C. To date, temperature-sensitive C-terminal truncations of Tfbl are the only TFIIH mutations that result in intermediate UV sensitivity, which might indicate a deficiency in either the global NER or TCR pathways. We have directly analyzed both TCR and global NER in these mutants. We found that ssl1, rad3 and tfb1 mutants, like rad25(ssl2-xp) mutants, are deficient in both the global NER and TCR pathways. Our results support the view that the mutations in any one of the genes encoding subunits of TFIIH result in deficiencies in both global and TCR pathways of NER. We suggest that when subunits of TFIIH are in limiting amounts, TCR may preclude global NER.