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  • Title: Trans-dominant inhibition of poly(ADP-ribosyl)ation potentiates carcinogen induced gene amplification in SV40-transformed Chinese hamster cells.
    Author: Kupper JH, Müller M, Bürkle A.
    Journal: Cancer Res; 1996 Jun 15; 56(12):2715-7. PubMed ID: 8665500.
    Abstract:
    Poly(ADP-ribose) polymerase (PARP) is an evolutionally conserved nuclear protein present in most eukaryotic species and catalyzes the formation of ADP-ribose polymers covalently attached to proteins. PARP is strongly activated by DNA single- or double-strand breaks and is thought to be involved in cellular responses to DNA damage. Based on the SV40-transformed Chinese hamster cell line CO60, we had established stable transfectants that overexpress the PARP DNA-binding domain conditionally. DNA-binding domain overexpression led to trans-dominant inhibition of poly(ADP-ribosyl)ation and sensitized the cells to genotoxic agents. Using the amplification of chromosomally integrated SV40 DNA as an indicator system, we show here that trans-dominant PARP inhibition potentiates genetic instability induced by N-methyl-N'-nitro-N-nitrosoguanidine treatment of cells.
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