Erratic expression of DNA polymerases by beta-amyloid causes neuronal death.

Agata Copani, Maria Angela Sortino, Andrea Caricasole, S. Chiechio, Mariangela Chisari, Giuseppe Battaglia, Anna Maria Giuffrida-Stella, Carlo Vancheri, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

An ectopic reentrance into the cell cycle with ensuing DNA replication is required for neuronal apoptosis induced by beta-amyloid. Here, we investigate the repertoire of DNA polymerases expressed in beta-amyloid-treated neurons, and their specific role in DNA synthesis and apoptosis. We show that exposure of cultured cortical neurons to beta-amyloid induces the expression of DNA polymerase-beta, proliferating cell nuclear antigen, and the p49 and p58 subunits of DNA primase. Induction requires the activity of cyclin-dependent kinases. The knockdown of the p49 primase subunit prevents beta-amyloid-induced neuronal DNA synthesis and apoptosis. Similar effects are observed by knocking down DNA polymerase-beta or by using dideoxycytidine, a preferential inhibitor of this enzyme. Thus, the reparative enzyme DNA polymerase-beta unexpectedly mediates a large component of de novo DNA synthesis and apoptotic death in neurons exposed to beta-amyloid. These data indicate that DNA polymerases become death signals when erratically expressed by differentiated neurons.

Original languageEnglish
Pages (from-to)2006-2008
Number of pages3
JournalFASEB Journal
Volume16
Issue number14
Publication statusPublished - 2002

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    Copani, A., Sortino, M. A., Caricasole, A., Chiechio, S., Chisari, M., Battaglia, G., Giuffrida-Stella, A. M., Vancheri, C., & Nicoletti, F. (2002). Erratic expression of DNA polymerases by beta-amyloid causes neuronal death. FASEB Journal, 16(14), 2006-2008.