Eukaryotic cells are able to mount several genetically complex cellular responses to DNA damage. The yeast Saccharomyces cerevisiae is a genetically well characterized organism that is also amenable to molecular and biochemical studies. Hence, this organism has provided a useful and informative model for dissecting the biochemistry and molecular biology of DNA repair in eukaryotes.

Cockayne syndrome is a rare autosomal recessive disease characterized by a complex clinical phenotype. Most Cockayne syndrome cells are hypersensitive to killing by ultraviolet radiation. This observation has prompted a wealth of studies on the DNA repair capacity of Cockayne syndrome cells in vitro. Many studies support the notion that such cells are defective in a DNA repair mode(s) that is transcription‐dependent. However, it remains to be established that this is a primary molecular defect in Cockayne syndrome cells and that (...) it explains the complex clinical phenotype associated with the disease. An alternative hypothesis is that Cockayne syndrome cells have a defect in transcription affecting the expression of certain genes, which is compatible with embryogenesis but not with normal post‐natal development. Defective transcription may impair the normal processing of DNA damage during transcription‐dependent repair.‘“Curiouser and curiouser” cried Alice.’ (Lewis Carroll, Alice's Adventures in Wonderland). (shrink)

The skin‐cancer‐prone hereditary disease xeroderma pigmentosum is typically characterized by defective nucleotide excision repair (NER) of DNA. However, since all subunits of the core basal transcription factor TFIIH are required for both RNA polymerase II basal transcription and NER, some mutations affecting genes that encode TFIIH subunits can result in clinical phenotypes associated with defective basal transcription. Among these is a syndrome called trichothiodystrophy (TTD) in which the prominent features are brittle hair and nails, and dry scaly skin. A recent (...) study provides dramatic support for the so‐called transcription hypothesis of TTD.(1) Specifically, several patients have been shown to carry a mutation in the XPD gene, which encodes a thermolabile form of XPD protein, resulting in loss of hair during febrile episodes. BioEssays 23:671–673, 2001. © 2001 John Wiley & Sons, Inc. (shrink)