TRF2 promotes dynamic and stepwise looping of POT1 bound telomeric overhang

• Published in: Nucleic acids research Vol. 49; no. 21; pp. 12377 - 12393
• Main Authors: Paul, Tapas, Liou, Wilson, Cai, Xinyi, Opresko, Patricia L, Myong, Sua
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 02.12.2021
• Subjects: Fluorescence Resonance Energy Transfer - methods; Fluorescent Dyes - chemistry; Fluorescent Dyes - metabolism; Humans; Microscopy, Fluorescence - methods; Molecular Biology; Protein Binding; Recombinant Proteins - metabolism; Shelterin Complex - genetics; Shelterin Complex - metabolism; Telomere - genetics; Telomere - metabolism; Telomere-Binding Proteins - genetics; Telomere-Binding Proteins - metabolism; Telomeric Repeat Binding Protein 2 - genetics; Telomeric Repeat Binding Protein 2 - metabolism; Tripeptidyl-Peptidase 1 - genetics; Tripeptidyl-Peptidase 1 - metabolism
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkab1123

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.