LOSS OF THE XERODERMA-PIGMENTOSUM GROUP-A GENE (XPA) ENHANCES APOPTOSIS OF CULTURED CEREBELLAR NEURONS INDUCED BY UV BUT NOT BY LOW-K+ MEDIUM

To study the involvement of the xeroderma pigmentosum group A gene (XP A) in neuronal apoptosis, we cultured cerebellar neurons from mice lac king XPA gene (XPA(-/-)) and induced apoptosis by exposure to UV irrad iation or medium containing a low concentration of potassium (low-K+ m edium). When cerebellar neurons from postnatal days 15-16 wild-type mi ce were treated with UV irradiation, apoptotic neuronal death was obse rved after 24-48 h. About 60% of neurons survived 48 h after UV irradi ation at a dose of 5 J/m(2). On the other hand, neurons from XPA(-/-) mice showed a significantly increased vulnerability to UV irradiation, and >90% of neurons died 48 h after UV irradiation at a dose of 5 J/m (2). In contrast, low-K+ medium induced apoptosis of neurons from mice of each genotype with the same kinetics. These results suggest that t he XPA gene is involved in neuronal DNA repair and that it thereby inf luences apoptosis induced by DNA damage in cultured cerebellar neurons .