The G-rich single stranded DNA (ssDNA) at 3' end of human telomeres self-folds into G-quaduplex (GQ) that may modulate the overhang accessibility to telomerase and proteins associated with the alternative lengthening of telomeres (ALT). We report that the telomeric overhang exhibits dynamic property when the repeat length exceeds four TTAGGG.  We find that the four and eight repeats of TTAGGG overhang that can fold into one and two GQs respectively, yield limited accessibility to complementary DNA, RAD51, RPA, WRN, BLM and telomerase whereas five to seven repeats render substantially higher accessibility (7>6>5). The same pattern is reflected in the telomerase extension activity. In contrast, POT1, a telomere specific binding protein, associates with telomeric overhang independent of the repeat length. Our results reveal a regulatory function of the telomeric overhang length and dynamics that may contribute to the telomere extension.

Telomere overhang accessibility to telomerase and ALT associated proteins is repeat length dependent

246th National Meeting (2013)

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