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Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation

Protection of telomeres (POT1) binds chromosome ends, recognizing single-strand telomeric DNA via two oligonucleotide/oligosaccharide binding folds (OB-folds). The Arabidopsis thaliana POT1a and POT1b paralogs are atypical: they do not exhibit telomeric DNA binding, and they have opposing roles in r...

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Autores principales: Arora, Amit, Beilstein, Mark A., Shippen, Dorothy E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175356/
https://www.ncbi.nlm.nih.gov/pubmed/27651456
http://dx.doi.org/10.1093/nar/gkw807
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author Arora, Amit
Beilstein, Mark A.
Shippen, Dorothy E.
author_facet Arora, Amit
Beilstein, Mark A.
Shippen, Dorothy E.
author_sort Arora, Amit
collection PubMed
description Protection of telomeres (POT1) binds chromosome ends, recognizing single-strand telomeric DNA via two oligonucleotide/oligosaccharide binding folds (OB-folds). The Arabidopsis thaliana POT1a and POT1b paralogs are atypical: they do not exhibit telomeric DNA binding, and they have opposing roles in regulating telomerase activity. AtPOT1a stimulates repeat addition processivity of the canonical telomerase enzyme, while AtPOT1b interacts with a regulatory lncRNA that represses telomerase activity. Here, we show that OB1 of POT1a, but not POT1b, has an intrinsic affinity for telomeric DNA. DNA binding was dependent upon a highly conserved Phe residue (F65) that in human POT1 directly contacts telomeric DNA. F65A mutation of POT1a(OB1) abolished DNA binding and diminished telomerase repeat addition processivity. Conversely, AtPOT1b and other POT1b homologs from Brassicaceae and its sister family, Cleomaceae, naturally bear a non-aromatic amino acid at this position. By swapping Val (V63) with Phe, AtPOT1b(OB1) gained the capacity to bind telomeric DNA and to stimulate telomerase repeat addition processivity. We conclude that, in the context of DNA binding, variation at a single amino acid position promotes divergence of the AtPOT1b paralog from the ancestral POT1 protein.
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spelling pubmed-51753562016-12-27 Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation Arora, Amit Beilstein, Mark A. Shippen, Dorothy E. Nucleic Acids Res Molecular Biology Protection of telomeres (POT1) binds chromosome ends, recognizing single-strand telomeric DNA via two oligonucleotide/oligosaccharide binding folds (OB-folds). The Arabidopsis thaliana POT1a and POT1b paralogs are atypical: they do not exhibit telomeric DNA binding, and they have opposing roles in regulating telomerase activity. AtPOT1a stimulates repeat addition processivity of the canonical telomerase enzyme, while AtPOT1b interacts with a regulatory lncRNA that represses telomerase activity. Here, we show that OB1 of POT1a, but not POT1b, has an intrinsic affinity for telomeric DNA. DNA binding was dependent upon a highly conserved Phe residue (F65) that in human POT1 directly contacts telomeric DNA. F65A mutation of POT1a(OB1) abolished DNA binding and diminished telomerase repeat addition processivity. Conversely, AtPOT1b and other POT1b homologs from Brassicaceae and its sister family, Cleomaceae, naturally bear a non-aromatic amino acid at this position. By swapping Val (V63) with Phe, AtPOT1b(OB1) gained the capacity to bind telomeric DNA and to stimulate telomerase repeat addition processivity. We conclude that, in the context of DNA binding, variation at a single amino acid position promotes divergence of the AtPOT1b paralog from the ancestral POT1 protein. Oxford University Press 2016-11-16 2016-09-19 /pmc/articles/PMC5175356/ /pubmed/27651456 http://dx.doi.org/10.1093/nar/gkw807 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 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 journals.permissions@oup.com
spellingShingle Molecular Biology
Arora, Amit
Beilstein, Mark A.
Shippen, Dorothy E.
Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation
title Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation
title_full Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation
title_fullStr Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation
title_full_unstemmed Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation
title_short Evolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation
title_sort evolution of arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175356/
https://www.ncbi.nlm.nih.gov/pubmed/27651456
http://dx.doi.org/10.1093/nar/gkw807
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