Poster abstracts

Poster number 143 submitted by Hamza Balci

Single Molecule Investigations on Accessibility of Long Telomeric Overhangs

Hamza Balci (Physics Department, Kent State University), Sajad Shiekh (Physics Department, Kent State University), Amanda Jack (University of California, Berkeley), Sineth Kodikara (Physics Department, Kent State University), Janan Alfehaid (Physics Department, Kent State University), Ahmet Yildiz (University of California, Berkeley)

Abstract:
WWe present single molecule (including FRET, FRET-PAINT, PIFE, and Mass Photometry) studies that probe the folding patterns and accessibilities of telomeric overhangs of physiologically relevant lengths (up to 28 GGGTTA repeats). In particular, we investigate the impact of Shelterin complex and POT1 on the accessibility and protection of these otherwise vulnerable genomic regions. In addition to length-dependent periodic accessibility patterns, we present the impact of POT1 and Shelterin on these accessibility patterns. Our studies also illustrate the junction between single and double stranded telomeres to be highly accessible in the absence of shelterin. We present our recent work in which we focused on this junction region to understand the minimum requirements to attain effective protection by Shelterin or POT1, and the impact of 5'-phosphorylation of the junction region and sequence variations on protection of this region. We also investigated the impact of crowding agents on telomeric overhang compactness and accessibility. Finally, we present mass photometry experiments that directly probe binding of POT1, RPA and the Shelterin complex to such long telomeric overhangs.

References:
1- G. Mustafa, …, H. Balci, "Impact of Molecular Crowding on Accessibility of Telomeric Overhangs Forming Multiple G-quadruplexes" Biomacromolecules (2025), DOI:10.1021/acs.biomac.5c00360
2- S. Shiekh, …, H. Balci, "Protection of the Telomeric Junction by the Shelterin Complex", JACS (2024), DOI:10.1021/jacs.4c08649
3- Sineth G. Kodikara, …, H. Balci, "Detecting Secondary Structure Formation with FRET-PAINT", RSC-Analyst (2023) DOI: 10.1039/d3an01118f
4- S. Shiekh, …, H. Balci, "Shelterin reduces the accessibility of telomeric overhangs", NAR (2022). DOI: 10.1093/nar/gkac1176
5- S. Shiekh, …, H. Balci, "Emerging Accessibility Patterns in Long Telomeric Overhangs", PNAS (2022), DOI: 10.1073/pnas.2202317119

Keywords: Telomere, G-quadruplex, Shelterin