Cockayne syndrome (complementation groups A and B) is a rare autosomal recessive DNA repair disorder characterized by photosensitive skin and severely impaired physical and intellectual development. The
Cockayne syndrome A and B
proteins intervene in the repair of
DNA modifications that block the
RNA polymerase in transcribed DNA sequences (transcription-coupled repair). Recent results suggest that they also have a more general role in the repair of oxidative
DNA base modifications. Although the phenotypical consequences of defective repair of oxidatively damaged
DNA in
Cockayne syndrome are not determined, accumulation of oxidized lesions might contribute to delay the physical and intellectual development of these patients. To conceive new therapeutic strategies for this syndrome, we are investigating whether the oxidatively damaged DNA repair defect in
Cockayne syndrome might be complemented by heterologous repair
proteins, such as the Escherichia coli
formamidopyrimidine-DNA glycosylase and
endonuclease III. The complementation studies may shed light on the important lesions for the
Cockayne syndrome phenotype and offer new tools for future
therapies aimed at counteracting the consequences of oxidatively damaged
DNA accumulation.