Detection of excision nuclease in cell-free extracts from the adult mammalian brain.

The autosomal recessive disorder xeroderma pigmentosum (XP) results from defects in the nucleotide excision repair (NER) pathway for DNA repair. NER normally repairs bulky DNA lesions, such as pyrimidine dimers resulting from UV radiation. XP patients have high rates of skin cancer, and some also develop progressive neurological degeneration. To better understand the mechanism of this neurodegeneration, I used a specific assay for the multicomponent excision nuclease of the NER pathway in cell-free extracts from the adult rat brain. Excision nuclease activity was detectable in whole-cell extracts prepared from the cerebellum, whereas extracts prepared from the forebrain, which has a lower density of cell nuclei, had much less activity. Nuclear extracts from both areas were equally capable of restoring activity to extracts from two different NER-deficient cell lines, despite large differences in the ratio of neurons to nonneuronal cells in the cerebellum and forebrain. These results indicate that the NER pathway is functional in neuronal cells in the adult brain. The implications of this finding for XP and other neurodegenerative diseases is discussed.