Platination of telomeric DNA by cisplatin disrupts recognition by TRF2 and TRF1

Isabelle Ourliac-Garnier 1, 2 Anaïs Poulet 3, 4 Razan Charif 1, 5 Simon Amiard 3 Frédérique Magdinier 4 Keyvan Rezai 6 Eric Gilson 4 Marie-Josèphe Giraud-Panis 3, 4 Sophie Bombard 1, 5
1 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques
2 Telomeres and Cancer Laboratory
3 Laboratoire Joliot Curie
4 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
5 U1007 - Homéostasie cellulaire et cancer - Reprogrammation des réponses biologiques et thérapies alternatives
6 Department of Pharmacology Oncology
Abstract : Telomeres, the nucleoprotein complexes located at the ends of chromosomes, are involved in chromosome protection and genome stability. Telomeric repeat binding factor 1 (TRF1) and telomeric repeat binding factor 2 (TRF2) are the two telomeric proteins that bind to duplex telomeric DNA through interactions between their C-terminal domain and several guanines of the telomeric tract. Since the antitumour drug cisplatin binds preferentially to two adjacent guanines, we have investigated whether cisplatin adducts could affect the binding of TRF1 and TRF2 to telomeric DNA and the property of TRF2 to stimulate telomeric invasion, a process that is thought to participate in the formation of the t-loop. We show that the binding of TRF1 and TRF2 to telomeric sequences selectively modified by one GG chelate of cisplatin is markedly affected by cisplatin but that the effect is more drastic for TRF2 than for TRF1 (3-5-fold more sensitivity for TRF2 than for TRF1). We also report that platinum adducts cause a decrease in TRF2-dependent stimulation of telomeric invasion in vitro. Finally, in accordance with in vitro data, analysis of telomeric composition after cisplatin treatment reveals that 60% of TRF2 dissociate from telomeres.
Keywords : Telomeres TRF1 TRF2 Cisplatin Antitumour
Document type :
Journal articles
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https://hal-ens-lyon.archives-ouvertes.fr/ensl-00817412
Contributor : Agnès Ganivet <>
Submitted on : Wednesday, April 24, 2013 - 3:28:02 PM
Last modification on : Wednesday, December 4, 2019 - 10:30:07 AM

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  • HAL Id : ensl-00817412, version 1
  • DOI : 10.1007

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Isabelle Ourliac-Garnier, Anaïs Poulet, Razan Charif, Simon Amiard, Frédérique Magdinier, et al.. Platination of telomeric DNA by cisplatin disrupts recognition by TRF2 and TRF1. Journal of Biological Inorganic Chemistry, Springer Verlag, 2010, 15 (5), pp.641-654. ⟨10.1007⟩. ⟨ensl-00817412⟩

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