XERODERMA-PIGMENTOSUM, COCKAYNE-SYNDROME AND TRICHOTHIODYSTROPHY - DOTHE GENES EXPLAIN THE DISEASES

Xeroderma pigmentosum Cockayne syndrome and trichothiodystrophy are th ree distinct human syndromes associated with sensitivity to ultraviole t radiation We review evidence that these syndromes overlap with each other and arise from mutations in genes involved in nucleotide-excisio n repair and RNA transcription Attempts have been made to explain the syndromes in terms of defects in repair and transcription These two bi ochemical pathways do not easily account for all the features of the s yndromes. Therefore, we propose a third pathway, in which the syndrome s are due, in part, to defects in a demethylation mechanism involving the excision of methylated cytosine. Perturbation of demethylation cou ld affect the developmentally regulated expression of some genes.