DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP

Maximilian Mimmler, Simon Peter, Alexander Kraus, Svenja Stroh, Teodora Nikolova, Nina Seiwert, Solveig Hasselwander, Carina Neitzel, Jessica Haub, Bernhard H. Monien, Petra Nicken, Pablo Steinberg, Jerry W. Shay, Bernd Kaina & Jörg Fahrer
PhIP is an abundant heterocyclic aromatic amine (HCA) and important dietary carcinogen. Following metabolic activation, PhIP causes bulky DNA lesions at the C8-position of guanine. Although C8-PhIP-dG adducts are mutagenic, their interference with the DNA replication machinery and the elicited DNA damage response (DDR) have not yet been studied. Here, we analyzed PhIP-triggered replicative stress and elucidated the role of the apical DDR kinases ATR, ATM and DNA-PKcs in the cellular defense response. First, we...
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