Telomerase recruitment by the telomere end binding protein-beta facilitates G-quadruplex DNA unfolding in ciliates

The telomeric G-overhangs of the ciliate Stylonychia lemnae fold into a G-quadruplex DNA structure in vivo. Telomeric G-quadruplex formation requires the presence of two telomere end binding proteins, TEBPalpha and TEBPbeta, and is regulated in a cell-cycle dependent manner. Unfolding of this structure in S phase is dependent on the phosphorylation of TEBPbeta. Here we show that TEBPbeta phosphorylation is necessary but not sufficient for a G-quadruplex unfolding rate compatible with telomere synthesis. The telomerase seems to be actively involved in telomeric G-quadruplex DNA structure unfolding in vivo. Significantly, the telomerase is recruited to telomeres by phosphorylated TEBPbeta, and hence telomerase recruitment is cell-cycle regulated through phosphorylation. These observations allow us to propose a model for the regulation of G-quadruplex unfolding and telomere synthesis during the cell cycle.