Altered biochemical specificity of G-quadruplexes with mutated tetrads

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Altered biochemical specificity of G-quadruplexes with mutated tetrads

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Title: Altered biochemical specificity of G-quadruplexes with mutated tetrads
Author: Švehlová, Kateřina; Lawrence, Michael S.; Bednárová, Lucie; Curtis, Edward A.

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Citation: Švehlová, Kateřina, Michael S. Lawrence, Lucie Bednárová, and Edward A. Curtis. 2016. “Altered biochemical specificity of G-quadruplexes with mutated tetrads.” Nucleic Acids Research 44 (22): 10789-10803. doi:10.1093/nar/gkw987. http://dx.doi.org/10.1093/nar/gkw987.
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Abstract: A fundamental motif in canonical nucleic acid structure is the base pair. Mutations that disrupt base pairs are typically destabilizing, but stability can often be restored by a second mutation that replaces the original base pair with an isosteric variant. Such concerted changes are a way to identify helical regions in secondary structures and to identify new functional motifs in sequenced genomes. In principle, such analysis can be extended to non-canonical nucleic acid structures, but this approach has not been utilized because the sequence requirements of such structures are not well understood. Here we investigate the sequence requirements of a G-quadruplex that can both bind GTP and promote peroxidase reactions. Characterization of all 256 variants of the central tetrad in this structure indicates that certain mutations can compensate for canonical G-G-G-G tetrads in the context of both GTP-binding and peroxidase activity. Furthermore, the sequence requirements of these two motifs are significantly different, indicating that tetrad sequence plays a role in determining the biochemical specificity of G-quadruplex activity. Our results provide insight into the sequence requirements of G-quadruplexes, and should facilitate the analysis of such motifs in sequenced genomes.
Published Version: doi:10.1093/nar/gkw987
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159562/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29739099
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