2 research outputs found
Association of a Platinum Complex to a G‑Quadruplex Ligand Enhances Telomere Disruption
Telomeres protect
the ends of chromosomes against illegitimate
recombination and repair. They can be targets for G-quadruplex ligands
and platinum complexes due to their repeated G-rich sequences. Protection
of telomeres is ensured by a complex of six proteins, including TRF2,
which inhibits the DNA damage response pathway. We analyzed telomere
modifications induced in cancer cells by the experimental hybrid platinum
complex, Pt-MPQ, comprising both an ethylene diamine monofunctional
platinum complex and a G-quadruplex recognition moiety (MPQ). Pt-MPQ
promotes the displacement of two telomeric proteins (TRF2 and TRF1)
from telomeres, as well as the formation of telomere damage and telomere
sister losses, whereas the control compound MPQ does not. This suggests
that the platinum moiety potentiates the targeting of the G-quadruplex
ligand to telomeres, opening a new perspective for telomere biology
and anticancer therapy. Interestingly, the chemotherapy drug cisplatin,
which has no specific affinity for G-quadruplex structures, partially
induces the TRF2 delocalization from telomeres but produces less telomeric
DNA damage, suggesting that this TRF2 displacement could be independent
of G-quadruplex recognition