24836024

PMC4067947

The G-rich single-stranded DNA at the 3' end of human telomeres can self-fold into G-quaduplex (GQ). However, telomere lengthening by telomerase or the recombination-based alternative lengthening of telomere (ALT) mechanism requires protein loading on the overhang. Using single-molecule fluorescence spectroscopy, we discovered that lengthening the telomeric overhang also increased the rate of dynamic exchanges between structural conformations. Overhangs with five to seven TTAGGG repeats, compared with four repeats, showed much greater dynamics and accessibility to telomerase binding and activity and loading of the ALT-associated proteins RAD51, WRN, and BLM. Although the eight repeats are highly dynamic, they can fold into two GQs, which limited protein accessibility. In contrast, the telomere-specific protein POT1 is unique in that it binds independently of repeat number. Our results suggest that the telomeric overhang length and dynamics may contribute to the regulation of telomere extension via telomerase action and the ALT mechanism.

CDC Public Access

343 NIH 1 DP2 GM105453 A/DP/NCCDPHP CDC HHS/United States
DP2 GM105453/GM/NIGMS NIH HHS/United States
ES0515052/ES/NIEHS NIH HHS/United States
F30 CA174323/CA/NCI NIH HHS/United States
R01 ES015052/ES/NIEHS NIH HHS/United States
R01 ES015632/ES/NIEHS NIH HHS/United States
R01 ES015632/ES/NIEHS NIH HHS/United States
R01GM65484/GM/NIGMS NIH HHS/United States
UL1 TR000142/TR/NCATS NIH HHS/United States