Cross-Links of Quadruplex Structures from Human Telomeric DNA by Dinuclear Platinum Complexes Show the Flexibility of Both Structures
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- 作者：Isabelle Ourliac-Garnier ; Miguel-Angel Elizondo-Riojas ; Sophie Redon ; Nicholas P. Farrell ; and Sophie Bombard
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：August 9, 2005
- 年：2005
- 卷：44
- 期：31
- 页码：10620 - 10634
- 全文大小：916K
- 年卷期：v.44,no.31(August 9, 2005)
- ISSN：1520-4995
文摘
The folding of AG3(T2AG3)3 was investigated in the presence of Na+ or K+ ions, by using thedinuclear platinum complexes [{trans-PtCl(NH3)2}2H2N(CH2)nNH2]Cl2 (n = 2 or 6). AG3(T2AG3)3 hasbeen previously found to adopt two different quadruplex structures: the antiparallel one in a solutioncontaining Na+ and the parallel one in a K+-containing crystal. The two structures are strikingly distinctand are not expected to form the same platinum cross-links. Therefore, characterization of the cross-linksformed with platinum complexes in solution allowed the predominant conformation(s) to be identified.The bases coordinating the platinum atoms were identified by chemical and 3'-exonuclease digestions.The observed cross-links showed that the parallel structure exists in solution whatever the cation andconfirmed the existence of the antiparallel structure in the presence of both cations as previously reportedfrom cross-linking experiments of AG3(T2AG3)3 by mononuclear platinum complexes. Furthermore, themajor platinum cross-links were unexpectedly formed between two guanines belonging to the sameG-quartet. Their formation was rationalized using molecular dynamics simulations in implicit solvent ofthe two quadruplex structures. It was shown that they were flexible, allowing some guanines to leavereversibly the top G-quartet and thus rendering their N7 atom accessible to platinum complexes. Ourresults also suggest that the human telomere sequence could be a target for such platinum complexes.