Autor según el artículo: Pelletier J., Riaño-Canalias F., Almacellas E., Mauvezin C., Samino S., Feu S., Menoyo S., Domostegui A., Garcia-Cajide M., Salazar R., Cortés C., Marcos R., Tauler A., Yanes O., Agell N., Kozma S.C., Gentilella A., Thomas G.

Departamento: Enginyeria Electrònica, Elèctrica i Automàtica

Autor/es de la URV: SAMINO GENÉ, SARA / Yanes Torrado, Óscar

Palabras clave: Suppression S-phase Rna-synthesis Proliferation P53 P21 Nucleotides Myc Metabolism Irbc Impdh Dna-damage Cell-cycle arrest Cancer Activation p21 nucleotides impdh irbc

Resumen: ©2020 The Authors. Published under the terms of the CC BY 4.0 license Many oncogenes enhance nucleotide usage to increase ribosome content, DNA replication, and cell proliferation, but in parallel trigger p53 activation. Both the impaired ribosome biogenesis checkpoint (IRBC) and the DNA damage response (DDR) have been implicated in p53 activation following nucleotide depletion. However, it is difficult to reconcile the two checkpoints operating together, as the IRBC induces p21-mediated G1 arrest, whereas the DDR requires that cells enter S phase. Gradual inhibition of inosine monophosphate dehydrogenase (IMPDH), an enzyme required for de novo GMP synthesis, reveals a hierarchical organization of these two checkpoints. We find that the IRBC is the primary nucleotide sensor, but increased IMPDH inhibition leads to p21 degradation, compromising IRBC-mediated G1 arrest and allowing S phase entry and DDR activation. Disruption of the IRBC alone is sufficient to elicit the DDR, which is strongly enhanced by IMPDH inhibition, suggesting that the IRBC acts as a barrier against genomic instability.

Áreas temáticas: Neuroscience (miscellaneous) Neuroscience (all) Molecular biology Medicine (miscellaneous) Medicina ii Immunology and microbiology (miscellaneous) Immunology and microbiology (all) General neuroscience General immunology and microbiology General biochemistry,genetics and molecular biology Ciências biológicas ii Ciências biológicas i Cell biology Biotecnología Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Biochemistry & molecular biology

Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/

Direcció de correo del autor: oscar.yanes@urv.cat

Identificador del autor: 0000-0003-3695-7157

Fecha de alta del registro: 2023-02-19

Versión del articulo depositado: info:eu-repo/semantics/publishedVersion

Enlace a la fuente original: https://www.embopress.org/doi/full/10.15252/embj.2019103838

URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/

Referencia al articulo segun fuente origial: Embo Journal. 39 (e103838): e103838-

Referencia de l'ítem segons les normes APA: Pelletier J., Riaño-Canalias F., Almacellas E., Mauvezin C., Samino S., Feu S., Menoyo S., Domostegui A., Garcia-Cajide M., Salazar R., Cortés C., Mar (2020). Nucleotide depletion reveals the impaired ribosome biogenesis checkpoint as a barrier against DNA damage. Embo Journal, 39(e103838), e103838-. DOI: 10.15252/embj.2019103838

DOI del artículo: 10.15252/embj.2019103838

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2020

Tipo de publicación: Journal Publications