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• W1936994465 endingPage "3163" @default.
• W1936994465 startingPage "3154" @default.
• W1936994465 abstract "Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins catalyzed by poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30), with NAD+ serving as the substrate. PARP is strongly activated upon recognition of DNA strand breaks by its DNA-binding domain. Experiments with low-molecular-weight inhibitors of PARP have led to the view that PARP activity plays a role in DNA repair and possibly also in DNA replication, cell proliferation, and differentiation. Accumulating evidence for nonspecific inhibitor effects prompted us to develop a molecular genetic system to inhibit PARP in living cells, i.e., to overexpress selectively the DNA-binding domain of PARP as a dominant negative mutant. Here we report on a cell culture system which allows inducible, high-level expression of the DNA-binding domain. Induction of this domain leads to about 90% reduction of poly(ADP-ribose) accumulation after gamma-irradiation and sensitizes cells to the cytotoxic effect of gamma-irradiation and of N-methyl-N'-nitro-N-nitrosoguanidine. In contrast, induction does not affect normal cellular proliferation or the replication of a transfected polyomavirus replicon. Thus, trans-dominant inhibition of the poly(ADP-ribose) accumulation occurring after gamma-irradiation or N-methyl-N'-nitro-N-nitrosoguanidine is specifically associated with a disturbance of the cellular recovery from the inflicted damage." @default.
• W1936994465 created "2016-06-24" @default.
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• W1936994465 date "1995-06-01" @default.
• W1936994465 modified "2023-09-23" @default.
• W1936994465 title "<i>trans</i>-Dominant Inhibition of Poly(ADP-Ribosyl)ation Sensitizes Cells against γ-Irradiation and <i>N</i>-Methyl-<i>N</i>′-Nitro-<i>N</i>-Nitrosoguanidine but Does Not Limit DNA Replication of a Polyomavirus Replicon" @default.
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• W1936994465 doi "https://doi.org/10.1128/mcb.15.6.3154" @default.
• W1936994465 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/230547" @default.
• W1936994465 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/7760811" @default.
• W1936994465 hasPublicationYear "1995" @default.
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