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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Qureshi, Mohammad H. Yildiz, Ahmet Balci, Hamza Ray, Sujay Bandaria, Jigar N. |
| Description | Author Affiliation: Ray S ( Departments of Physics and Biological Sciences, Kent State University, Kent, OH 44242.); |
| Abstract | Human telomeres terminate with a single-stranded 3' G overhang, which can be recognized as a DNA damage site by replication protein A (RPA). The protection of telomeres (POT1)/POT1-interacting protein 1 (TPP1) heterodimer binds specifically to single-stranded telomeric DNA (ssTEL) and protects G overhangs against RPA binding. The G overhang spontaneously folds into various G-quadruplex (GQ) conformations. It remains unclear whether GQ formation affects the ability of POT1/TPP1 to compete against RPA to access ssTEL. Using single-molecule Förster resonance energy transfer, we showed that POT1 stably loads to a minimal DNA sequence adjacent to a folded GQ. At 150 mM K(+), POT1 loading unfolds the antiparallel GQ, as the parallel conformation remains folded. POT1/TPP1 loading blocks RPA's access to both folded and unfolded telomeres by two orders of magnitude. This protection is not observed at 150 mM Na(+), in which ssTEL forms only a less-stable antiparallel GQ. These results suggest that GQ formation of telomeric overhangs may contribute to suppression of DNA damage signals. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Aminopeptidases Metabolism Dipeptidyl-Peptidases And Tripeptidyl-Peptidases G-Quadruplexes Models, Molecular Protein Conformation Replication Protein A Serine Proteases Telomere-Binding Proteins Telomere Chemistry Escherichia Coli Fluorescence Resonance Energy Transfer Microscopy, Fluorescence Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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