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Title: The expression of four pyridoxal kinase (PDXK) human variants in Drosophila impacts on genome integrity
Authors: Mascolo, Elisa
Barile, Anna
Mecarelli, Lorenzo Stufera
Amoroso, Noemi
Merigliano, Chiara
Massimi, Arianna
Saggio, Isabella
Hansen, Torben
Tramonti, Angela
Di Salvo, Martino Luigi
Barbetti, Fabrizio
Contestabile, Roberto
Vernì, Fiammetta
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Mascolo, E., Barile, A., Mecarelli, L. S., Amoroso, N., Merigliano, C., Massimi, A., . . . Vernì, F. (2019). The expression of four pyridoxal kinase (PDXK) human variants in Drosophila impacts on genome integrity. Scientific Reports, 9(1), 14188-. doi:10.1038/s41598-019-50673-4
Journal: Scientific reports
Abstract: In eukaryotes, pyridoxal kinase (PDXK) acts in vitamin B6 salvage pathway to produce pyridoxal 5'-phosphate (PLP), the active form of the vitamin, which is implicated in numerous crucial metabolic reactions. In Drosophila, mutations in the dPdxk gene cause chromosome aberrations (CABs) and increase glucose content in larval hemolymph. Both phenotypes are rescued by the expression of the wild type human PDXK counterpart. Here we expressed, in dPdxk1 mutant flies, four PDXK human variants: three (D87H, V128I and H246Q) listed in databases, and one (A243G) found in a genetic screening in patients with diabetes. Differently from human wild type PDXK, none of the variants was able to completely rescue CABs and glucose content elicited by dPdxk1 mutation. Biochemical analysis of D87H, V128I, H246Q and A243G proteins revealed reduced catalytic activity and/or reduced affinity for PLP precursors which justify this behavior. Although these variants are rare in population and carried in heterozygous condition, our findings suggest that in certain metabolic contexts and diseases in which PLP levels are reduced, the presence of these PDXK variants could threaten genome integrity and increase cancer risk.
ISSN: 2045-2322
DOI: 10.1038/s41598-019-50673-4
Schools: School of Biological Sciences 
Rights: © 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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