| http://purl.uniprot.org/citations/27558808 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27558808 | http://www.w3.org/2000/01/rdf-schema#comment | "Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)](2+) (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)](2+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing."xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.org/dc/terms/identifier | "doi:10.1038/srep31973"xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/author | "Vallis K.A."xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/author | "Ahmad H."xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/author | "Halder S."xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/author | "Ramadan K."xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/author | "Gill M.R."xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/author | "Boghozian R.A."xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/author | "Harun S.N."xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/name | "Sci Rep"xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/pages | "31973"xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/title | "A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition."xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://purl.uniprot.org/core/volume | "6"xsd:string |
| http://purl.uniprot.org/citations/27558808 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27558808 |
| http://purl.uniprot.org/citations/27558808 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27558808 |
| http://purl.uniprot.org/uniprot/#_O14757-mappedCitation-27558808 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27558808 |
| http://purl.uniprot.org/uniprot/O14757 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/27558808 |