First evidence of a functional ineraction between DNA quadruplexes and poly(ADP-ribose) polymerase-1

We discovered that the abundant human nuclear protein poly(ADP-ribose) polymerase-1 (hPARP-1) binds to intramolecular DNA quadruplexes in vitro with high affinity and with a stoichiometry of two proteins for one quadruplex. Using an enzymatic assay, we have shown that hPARP-1 gets catalytically activated upon binding to G-quadruplexes localized at the c-kit promoter and human telomere regions. This is the first example of a truly functional quadruplex-protein interaction, which has possible implications in understanding hPARP-1 mediated mechanisms of transcription regulation and telomere end protection.