Title
Consequences of altered poly(ADPribose) polymerase1 expression: Effects of altered PARP1 expression,Used
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Poly(ADPribosyl)ation is a posttranslational modification of cellular proteins mostly catalysed by poly(ADPribose) polymerase1 (PARP1) and to a lesser extent by PARP2. The study aimed to explore the role of PARP1 in DNA repair and cell death using in vitro as well as in vivo models and contributed to the potential use of a novel highlyselective PARP1 inhibitor, which provides a valuable tool to dissect different roles of PARP1 and PARP2 in cellular functions. Overexpression of human PARP1 (hPARP1) in rodent cells resulted in an increased DNA repair capacity after Xirradiation, but also to an increased susceptibility to DNA damage in response to alkylating agents or PARP inhibition. Novel transgenic mice with intended tissuespecific overexpression of hPARP1 were generated and characterized on a genetic level. Unexpectedly, despite cell culture validation of the expression construct and transgene expression on the mRNA level, no protein expression of the transgene could be detected in these mice for largely unknown reasons. This outcome needs to be considered in future approaches aiming to generate hPARP1 transgenic mice.
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