Nucleotide excision repair of DNA in eukaryotes: comparisons between human cells and yeast

Little is known about the molecular mechanism of nucleotide excision repair in eukaryotes. Studies on human cells have been stimulated by the availability of excision repair-defective cell lines from patients suffering from the autosomal recessive disease xeroderma pigmentosum. Such studies have contributed appreciably to an understanding of the genetic complexity of excision repair in human cells. However, to date no human excision repair genes or gene products known to complement the repair defect in xeroderma pigmentosum cells have been isolated. The yeast Saccharomyces cerevisiae is an interesting model for exploring the molecular mechanism of nucleotide excision repair in eukaryotic cells. As is true in human cells, multiple yeast genes are involved in this phenomenon and at least five genes are required for the specific incision of ultraviolet-irradiated DNA in vivo. These five genes have been isolated by molecular cloning and the nucleotide sequences of four of them have been determined. Each of these cloned genes will be used for overexpression of protein and it is anticipated that the purification and characterization of these proteins will provide insight into the biochemistry of nucleotide excision repair in eukaryotes.