Show simple item record

dc.contributor.authorArora, Amit
dc.contributor.authorBeilstein, Mark A.
dc.contributor.authorShippen, Dorothy E.
dc.date.accessioned2017-03-30T00:22:32Z
dc.date.available2017-03-30T00:22:32Z
dc.date.issued2016-09-19
dc.identifier.citationEvolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulation 2016:gkw807 Nucleic Acids Researchen
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.pmid27651456
dc.identifier.doi10.1093/nar/gkw807
dc.identifier.urihttp://hdl.handle.net/10150/622915
dc.description.abstractProtection 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. F65Amutation of POT1aOB1 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, AtPOT1bOB1 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.
dc.description.sponsorshipNIH [R01 GM065383]; NSF [MCB 1540273]en
dc.language.isoenen
dc.publisherOXFORD UNIV PRESSen
dc.relation.urlhttps://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkw807en
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/).en
dc.titleEvolution of Arabidopsis protection of telomeres 1 alters nucleic acid recognition and telomerase regulationen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Sch Plant Scien
dc.identifier.journalNucleic Acids Researchen
dc.description.noteOpen Access Journal.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-06-16T09:31:53Z
html.description.abstractProtection 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. F65Amutation of POT1aOB1 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, AtPOT1bOB1 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.


Files in this item

Thumbnail
Name:
gkw807.pdf
Size:
4.040Mb
Format:
PDF
Description:
Final Published Version

This item appears in the following Collection(s)

Show simple item record