A gene-nutrient interaction between vitamin B6 and serine hydroxymethyltransferase (SHMT) affects genome integrity in Drosophila.

Autor: Pilesi E; Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, Rome, Italy., Angioli C; Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, Rome, Italy., Graziani C; Department of Biochemical Sciences 'A. Rossi Fanelli', Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy., Parroni A; Department of Biochemical Sciences 'A. Rossi Fanelli', Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.; Institute of Molecular Biology and Pathology, National Research Council (IBPM-CNR), Rome, Italy., Contestabile R; Department of Biochemical Sciences 'A. Rossi Fanelli', Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy., Tramonti A; Department of Biochemical Sciences 'A. Rossi Fanelli', Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.; Institute of Molecular Biology and Pathology, National Research Council (IBPM-CNR), Rome, Italy., Vernì F; Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, Rome, Italy.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2023 Jul; Vol. 238 (7), pp. 1558-1566. Date of Electronic Publication: 2023 May 14.
DOI: 10.1002/jcp.31033
Abstrakt: Pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6, participates as a cofactor to one carbon (1C) pathway that produces precursors for DNA metabolism. The concerted action of PLP-dependent serine hydroxymethyltransferase (SHMT) and thymidylate synthase (TS) leads to the biosynthesis of thymidylate (dTMP), which plays an essential function in DNA synthesis and repair. PLP deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, rising the hypothesis that an altered 1C metabolism may be involved. To test this hypothesis, we used Drosophila as a model system and found, firstly, that in PLP deficient larvae SHMT activity is reduced by 40%. Second, we found that RNAi-induced SHMT depletion causes chromosome damage rescued by PLP supplementation and strongly exacerbated by PLP depletion. RNAi-induced TS depletion causes severe chromosome damage, but this is only slightly enhanced by PLP depletion. dTMP supplementation rescues CABs in both PLP-deficient and PLP-proficient SHMT RNAi . Altogether these data suggest that a reduction of SHMT activity caused by PLP deficiency contributes to chromosome damage by reducing dTMP biosynthesis. In addition, our work brings to light a gene-nutrient interaction between SHMT decreased activity and PLP deficiency impacting on genome stability that may be translated to humans.
(© 2023 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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