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|Title:||GGGCTA repeats can fold into hairpins poorly unfolded by replication protein A : a possible origin of the length-dependent instability of GGGCTA variant repeats in human telomeres||Authors:||Chatain, Jean
Phan, Anh Tuân
|Keywords:||Science::Biological sciences||Issue Date:||2021||Source:||Chatain, J., Blond, A., Phan, A. T., Saintomé, C. & Alberti, P. (2021). GGGCTA repeats can fold into hairpins poorly unfolded by replication protein A : a possible origin of the length-dependent instability of GGGCTA variant repeats in human telomeres. Nucleic Acids Research, 49(13), 7588-7601. https://dx.doi.org/10.1093/nar/gkab518||Journal:||Nucleic Acids Research||Abstract:||Human telomeres are composed of GGGTTA repeats and interspersed with variant repeats. The GGGCTA variant motif was identified in the proximal regions of human telomeres about 10 years ago and was shown to display a length-dependent instability. In parallel, a structural study showed that four GGGCTA repeats folded into a non-canonical G-quadruplex (G4) comprising a Watson-Crick GCGC tetrad. It was proposed that this non-canonical G4 might be an additional obstacle for telomere replication. In the present study, we demonstrate that longer GGGCTA arrays fold into G4 and into hairpins. We also demonstrate that replication protein A (RPA) efficiently binds to GGGCTA repeats structured into G4 but poorly binds to GGGCTA repeats structured into hairpins. Our results (along with results obtained with a more stable variant motif) suggest that GGGCTA hairpins are at the origin of GGGCTA length-dependent instability. They also suggest, as working hypothesis, that failure of efficient binding of RPA to GGGCTA structured into hairpins might be involved in the mechanism of GGGCTA array instability. On the basis of our present and past studies about telomeric G4 and their interaction with RPA, we propose an original point of view about telomeric G4 and the evolution of telomeric motifs.||URI:||https://hdl.handle.net/10356/153717||ISSN:||0305-1048||DOI:||10.1093/nar/gkab518||Rights:||© 2021 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact firstname.lastname@example.org||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SPMS Journal Articles|
Updated on May 20, 2022
Updated on May 20, 2022
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