TRF2 promotes dynamic and stepwise looping of POT1 bound telomeric overhang |
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| Authors: | Tapas Paul Wilson Liou Xinyi Cai Patricia L Opresko Sua Myong |
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| Institution: | Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA;Department of Environmental and Occupational Health, University of Pittsburgh, Hillman Cancer Center, 5117 Centre Avenue, Suite 2.6a, Pittsburgh, PA 15213, USA;Physics Frontier Center (Center for Physics of Living Cells), University of Illinois, 1110 W. Green St., Urbana, IL, 61801, USA |
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| Abstract: | Human telomeres are protected by shelterin proteins, but how telomeres maintain a dynamic structure remains elusive. Here, we report an unexpected activity of POT1 in imparting conformational dynamics of the telomere overhang, even at a monomer level. Strikingly, such POT1-induced overhang dynamics is greatly enhanced when TRF2 engages with the telomere duplex. Interestingly, TRF2, but not TRF2ΔB, recruits POT1-bound overhangs to the telomere ds/ss junction and induces a discrete stepwise movement up and down the axis of telomere duplex. The same steps are observed regardless of the length of the POT1-bound overhang, suggesting a tightly regulated conformational dynamic coordinated by TRF2 and POT1. TPP1 and TIN2 which physically connect POT1 and TRF2 act to generate a smooth movement along the axis of the telomere duplex. Our results suggest a plausible mechanism wherein telomeres maintain a dynamic structure orchestrated by shelterin. |
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