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Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the Drosophila warts (wts) Locus
Gnocchini, Eleonora; Pilesi, Eleonora; Schiano, Ludovica; Vernì, Fiammetta.
Afiliação
  • Gnocchini E; Department of Biology and Biotechnology "Charles Darwin", Sapienza University, 00185 Rome, Italy.
  • Pilesi E; Department of Biology and Biotechnology "Charles Darwin", Sapienza University, 00185 Rome, Italy.
  • Schiano L; Department of Biology and Biotechnology "Charles Darwin", Sapienza University, 00185 Rome, Italy.
  • Vernì F; Department of Biology and Biotechnology "Charles Darwin", Sapienza University, 00185 Rome, Italy.
Int J Mol Sci ; 23(11)2022 May 29.
Article em En | MEDLINE | ID: mdl-35682766
ABSTRACT
The active form of vitamin B6, pyridoxal 5'-phosphate (PLP), is a cofactor for more than 200 enzymes involved in many metabolic pathways. Moreover, PLP has antioxidant properties and quenches the reactive oxygen species (ROS). Accordingly, PLP deficiency causes chromosome aberrations in Drosophila, yeast, and human cells. In this work, we investigated whether PLP depletion can also cause loss of heterozygosity (LOH) of the tumor suppressor warts (wts) in Drosophila. LOH is usually initiated by DNA breakage in heterozygous cells for a tumor suppressor mutation and can contribute to oncogenesis inducing the loss of the wild-type allele. LOH at the wts locus results in epithelial wts homozygous tumors easily detectable on adult fly cuticle. Here, we found that PLP depletion, induced by two PLP inhibitors, promotes LOH of wts locus producing significant frequencies of wts tumors (~7% vs. 2.3%). In addition, we identified the mitotic recombination as a possible mechanism through which PLP deficiency induces LOH. Moreover, LOH of wts locus, induced by PLP inhibitors, was rescued by PLP supplementation. These data further confirm the role of PLP in genome integrity maintenance and indicate that vitamin B6 deficiency may impact on cancer also by promoting LOH.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Deficiência de Vitamina B 6 / Verrugas Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Deficiência de Vitamina B 6 / Verrugas Idioma: En Ano de publicação: 2022 Tipo de documento: Article