3 UNUSUAL REPAIR DEFICIENCIES ASSOCIATED WITH TRANSCRIPTION FACTOR BTF2(TFIIH) - EVIDENCE FOR THE EXISTENCE OF A TRANSCRIPTION SYNDROME

To counteract the deleterious effects of DNA damage, a sophisticated network of DNA repair systems has evolved, which is essential for genetic stability and prevention of carcinogenesis. Nucleotide excision repair (NER), one of the main repair pathways, can remove a wide range of lesions from the DNA by a complex multistep reaction (for a recent review, see Hoeijmakers 1993). Two subpathways are recognized in NER: a rapid "transcription-coupled" repair and the less efficient global genome repair (Bohr 1991; Hanawalt and Mellon 1993). The consequences of inborn errors in NER are highlighted by the prototype repair syndrome, xeroderma pigmentosum (XP), an autosomal recessive condition displaying sun (UV) sensitivity, pigmentation abnormalities, predisposition to skin cancer, and often progressive neurodegeneration (Cleaver and Kraemer 1994). Two other excision repair disorders have been recognized, Cockayne's syndrome (CS) and trichothiodystrophy (TTD), which present different clinical features.