Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the <i>Drosophila</i> <i>warts</i> (<i>wts</i>) Locus
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 <i>Dro...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/6087 |
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| author | Eleonora Gnocchini Eleonora Pilesi Ludovica Schiano Fiammetta Vernì |
| author_facet | Eleonora Gnocchini Eleonora Pilesi Ludovica Schiano Fiammetta Vernì |
| author_sort | Eleonora Gnocchini |
| collection | DOAJ |
| description | 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 <i>Drosophila</i>, yeast, and human cells. In this work, we investigated whether PLP depletion can also cause loss of heterozygosity (LOH) of the tumor suppressor <i>warts</i> (<i>wts</i>) in <i>Drosophila</i>. 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 <i>wts</i> locus results in epithelial <i>wts</i> homozygous tumors easily detectable on adult fly cuticle. Here, we found that PLP depletion, induced by two PLP inhibitors, promotes LOH of <i>wts</i> locus producing significant frequencies of <i>wts</i> 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 <i>wts</i> 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. |
| first_indexed | 2024-03-10T01:16:19Z |
| format | Article |
| id | doaj.art-a50a07666273435aa78c7052e5b85f78 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:16:19Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a50a07666273435aa78c7052e5b85f782023-11-23T14:09:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012311608710.3390/ijms23116087Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the <i>Drosophila</i> <i>warts</i> (<i>wts</i>) LocusEleonora Gnocchini0Eleonora Pilesi1Ludovica Schiano2Fiammetta Vernì3Department of Biology and Biotechnology “Charles Darwin”, Sapienza University, 00185 Rome, ItalyDepartment of Biology and Biotechnology “Charles Darwin”, Sapienza University, 00185 Rome, ItalyDepartment of Biology and Biotechnology “Charles Darwin”, Sapienza University, 00185 Rome, ItalyDepartment of Biology and Biotechnology “Charles Darwin”, Sapienza University, 00185 Rome, ItalyThe 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 <i>Drosophila</i>, yeast, and human cells. In this work, we investigated whether PLP depletion can also cause loss of heterozygosity (LOH) of the tumor suppressor <i>warts</i> (<i>wts</i>) in <i>Drosophila</i>. 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 <i>wts</i> locus results in epithelial <i>wts</i> homozygous tumors easily detectable on adult fly cuticle. Here, we found that PLP depletion, induced by two PLP inhibitors, promotes LOH of <i>wts</i> locus producing significant frequencies of <i>wts</i> 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 <i>wts</i> 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.https://www.mdpi.com/1422-0067/23/11/6087pyridoxal 5′ phosphate (PLP)vitamin B6loss of heterozygosity (LOH)mitotic recombination<i>warts</i><i>Drosophila</i> |
| spellingShingle | Eleonora Gnocchini Eleonora Pilesi Ludovica Schiano Fiammetta Vernì Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the <i>Drosophila</i> <i>warts</i> (<i>wts</i>) Locus International Journal of Molecular Sciences pyridoxal 5′ phosphate (PLP) vitamin B6 loss of heterozygosity (LOH) mitotic recombination <i>warts</i> <i>Drosophila</i> |
| title | Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the <i>Drosophila</i> <i>warts</i> (<i>wts</i>) Locus |
| title_full | Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the <i>Drosophila</i> <i>warts</i> (<i>wts</i>) Locus |
| title_fullStr | Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the <i>Drosophila</i> <i>warts</i> (<i>wts</i>) Locus |
| title_full_unstemmed | Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the <i>Drosophila</i> <i>warts</i> (<i>wts</i>) Locus |
| title_short | Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the <i>Drosophila</i> <i>warts</i> (<i>wts</i>) Locus |
| title_sort | vitamin b6 deficiency promotes loss of heterozygosity loh at the i drosophila i i warts i i wts i locus |
| topic | pyridoxal 5′ phosphate (PLP) vitamin B6 loss of heterozygosity (LOH) mitotic recombination <i>warts</i> <i>Drosophila</i> |
| url | https://www.mdpi.com/1422-0067/23/11/6087 |
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