DETECTION OF EXCISION NUCLEASE IN CELL-FREE-EXTRACTS FROM THE ADULT MAMMALIAN BRAIN

The autosomal recessive disorder xeroderma pigmentosum (XP) results fr om defects in the nucleotide excision repair (NER) pathway for DNA rep air. NER normally repairs bulky DNA lesions, such as pyrimidine dimers resulting from UV radiation. XP patients have high rates of skin canc er, and some also develop progressive neurological degeneration. To be tter understand the mechanism of this neurodegeneration, I used a spec ific assay for the multicomponent excision nuclease of the NER pathway in cell-free extracts from the adult rat brain. Excision nuclease act ivity was detectable in whole-cell extracts prepared from the cerebell um, whereas extracts prepared from the forebrain, which has a lower de nsity of cell nuclei, had much less activity. Nuclear extracts from bo th areas were equally capable of restoring activity to extracts from t wo different NER-deficient cell lines, despite large differences in th e ratio of neurons to nonneuronal cells in the cerebellum and forebrai n. These results indicate that the NER pathway is functional in neuron al cells in the adult brain. The implications of this finding for XP a nd other neurodegenerative diseases is discussed. (C) 1998 Elsevier Sc ience B.V. All rights reserved.