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A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition

Abstract:

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 ...

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Publication status:
Published
Peer review status:
Peer reviewed
Version:
Publisher's version

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Publisher copy:
10.1038/srep31973

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Department:
Oxford, MSD, Oncology, CRUK/MRC Ox Inst for Radiation Oncology
More by this author
Department:
Oxford, MSD, Oncology, CRUK/MRC Ox Inst for Radiation Oncology
More by this author
Department:
Oxford, MSD, Oncology, CRUK/MRC Ox Inst for Radiation Oncology
More by this author
Department:
Oxford, MSD, Oncology, CRUK/MRC Ox Inst for Radiation Oncology
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Funding agency for:
Halder, S
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Funding agency for:
Vallis, Katherine
Publisher:
Nature Publishing Group Publisher's website
Journal:
Scientific Reports Journal website
Volume:
6
Pages:
Article: 31973
Publication date:
2016
Acceptance date:
2016-08-01
DOI:
ISSN:
2045-2322
Pubs id:
pubs:638190
URN:
uri:93ddd8f3-a9d0-473d-ae69-90b4f7a793ed
UUID:
93ddd8f3-a9d0-473d-ae69-90b4f7a793ed
Local pid:
pubs:638190

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