دورية أكاديمية

Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the Drosophilawarts (wts) Locus

التفاصيل البيبلوغرافية
العنوان: Vitamin B6 Deficiency Promotes Loss of Heterozygosity (LOH) at the Drosophilawarts (wts) Locus
المؤلفون: Eleonora Gnocchini, Eleonora Pilesi, Ludovica Schiano, Fiammetta Vernì
المصدر: International Journal of Molecular Sciences; Volume 23; Issue 11; Pages: 6087
بيانات النشر: Multidisciplinary Digital Publishing Institute
سنة النشر: 2022
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: pyridoxal 5′ phosphate (PLP), vitamin B6, loss of heterozygosity (LOH), mitotic recombination, warts, Drosophila
جغرافية الموضوع: agris
الوصف: 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.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
العلاقة: Molecular Genetics and Genomics; https://dx.doi.org/10.3390/ijms23116087Test
DOI: 10.3390/ijms23116087
الإتاحة: https://doi.org/10.3390/ijms23116087Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.5E9F7D78
قاعدة البيانات: BASE