The G-Quadruplex Ligand Telomestatin Impairs Binding of Topoisomerase IIlα to G-Quadruplex-Forming Oligonucleotides and Uncaps Telomeres in ALT Cells.

Autor: Temime-Smaali, Nassima, Guittat, Lionel, Sidibe, Assitan, Shin-ya, Kazuo, Trentesaux, Chantal, Riou, Jean-François
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Zdroj: PLoS ONE; 2009, Vol. 4 Issue 9, p1-14, 14p, 3 Color Photographs, 4 Diagrams, 4 Graphs
Abstrakt: In Alternative Lengthening of Telomeres (ALT) cell lines, specific nuclear bodies called APBs (ALT-associated PML bodies) concentrate telomeric DNA, shelterin components and recombination factors associated with telomere recombination. Topoisomerase IIIa (Topo III) is an essential telomeric-associated factor in ALT cells. We show here that the binding of Topo III to telomeric G-overhang is modulated by G-quadruplex formation. Topo III binding to G-quadruplex-forming oligonucleotides was strongly inhibited by telomestatin, a potent and specific G-quadruplex ligand. In ALT cells, telomestatin treatment resulted in the depletion of the Topo III/BLM/TRF2 complex and the disruption of APBs and led to the segregation of PML, shelterin components and Topo III. Interestingly, a DNA damage response was observed at telomeres in telomestatin-treated cells. These data indicate the importance of G-quadruplex stabilization during telomere maintenance in ALT cells. The function of TRF2/Topo III/BLM in the resolution of replication intermediates at telomeres is discussed. [ABSTRACT FROM AUTHOR]
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