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Int. J. Mol. Sci. 2018, 19(7), 1951; https://doi.org/10.3390/ijms19071951

Platinum Complexes Can Bind to Telomeres by Coordination

1
INSERM UMR-S 1007, Cellular Homeostasis and Cancer, 75006 Paris, France
2
Paris Descartes University, Paris Sorbonne Cité, 75006 Paris, France
3
Paris Sud University, Paris-Saclay University, 91405 Orsay, France
4
Laboratoire de Toxicologie-Biologique, Hôpital Lariboisière, 2 rue Ambroise Paré, 75475 Paris, France
5
Institut Curie-Recherche, Bât. 112, Centre Universitaire, 91405 Orsay, France
6
CNRS UMR918, Centre Universitaire, 91405 Orsay, France
7
INSERM U1196, Centre Universitaire, 91405 Orsay, France
*
Authors to whom correspondence should be addressed.
Received: 17 May 2018 / Revised: 27 June 2018 / Accepted: 29 June 2018 / Published: 3 July 2018
(This article belongs to the Special Issue Platinum-Based Anti-Tumor Drugs)
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Abstract

It is suggested that several compounds, including G-quadruplex ligands, can target telomeres, inducing their uncapping and, ultimately, cell death. However, it has never been demonstrated whether such ligands can bind directly and quantitatively to telomeres. Here, we employed the property of platinum and platinum-G-quadruplex complexes to target G-rich sequences to investigate and quantify their covalent binding to telomeres. Using inductively coupled plasma mass spectrometry, surprisingly, we found that, in cellulo, in the presence of cisplatin, a di-functional platinum complex, telomeric DNA was platinated 13-times less than genomic DNA in cellulo, as compared to in vitro data. On the contrary, the amount of mono-functional platinum complexes (Pt-ttpy and Pt-tpy) bound either to telomeric or to genomic DNA was similar and occurred in a G-quadruplex independent-manner. Importantly, the quantification revealed that the low level of cisplatin bound to telomeric DNA could not be the direct physical cause of TRF2 displacement from telomeres. Altogether, our data suggest that platinum complexes can affect telomeres both directly and indirectly. View Full-Text
Keywords: telomeres; platinum complexes; cisplatin; G-quadruplex; TRF2 telomeres; platinum complexes; cisplatin; G-quadruplex; TRF2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Saker, L.; Ali, S.; Masserot, C.; Kellermann, G.; Poupon, J.; Teulade-Fichou, M.-P.; Ségal-Bendirdjian, E.; Bombard, S. Platinum Complexes Can Bind to Telomeres by Coordination. Int. J. Mol. Sci. 2018, 19, 1951.

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