Dihydropyrimidinase protects from DNA replication stress caused by cytotoxic metabolites.
作者： Jihane Basbous , Antoine Aze , Laurent Chaloin , Rana Lebdy , Dana Hodroj
DOI: 10.1093/NAR/GKZ1162
关键词: Biochemistry 、 Plasmid 、 Transcription (biology) 、 DNA 、 DNA replication 、 Dihydrothymine 、 Xenopus 、 Biology 、 Dihydropyrimidinase 、 Cancer cell
摘要: Imbalance in the level of pyrimidine degradation products dihydrouracil and dihydrothymine is associated with cellular transformation cancer progression. Dihydropyrimidines are degraded by dihydropyrimidinase (DHP), a zinc metalloenzyme that upregulated solid tumors but not corresponding normal tissues. How dihydropyrimidine metabolites affect phenotypes remains elusive. Here we show accumulation dihydropyrimidines induces formation DNA-protein crosslinks (DPCs) causes DNA replication transcriptional stress. We used Xenopus egg extracts to recapitulate invitro. found interfere directly both plasmid chromosomal DNA. Furthermore, plant flavonoid dihydromyricetin inhibits human DHP activity. Cellular exposure triggered DPCs-dependent stress cells. This study defines as potentially cytotoxic may offer an opportunity for therapeutic-targeting activity tumors.
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