Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression

Repair of UV-induced DNA lesions in terminally differentiated human hNT neu rons was compared to that in their repair-proficient precursor NT2 cells. G lobal genome repair of (6-4)pyrimidine pyrimidone photoproducts was signifi cantly slower in hNT neurons than in the precursor cells, and repair of cyc lobutane pyrimidine dimers (CPDs) was not detected in the hNT neurons, This deficiency in global genome repair did not appear to be due to denser chro matin structure in hNT neurons. By contrast, CPDs were removed efficiently from both strands of transcribed genes in hNT neurons, with the nontranscri bed strand being repaired unexpectedly well, Correlated with these changes in repair during neuronal differentiation were modifications in the express ion of several repair genes, in particular an up-regulation of the two stru cture-specific nucleases XPG and XPF/ERCC1, These results have implications for neuronal dysfunction and aging.