Artículo
Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans
Autor/es | Marsac, Roxane
Pinson, Benoît Saint-Marc, Christelle Olmedo López, María Artal Sanz, Marta Daignan-Fornier, Bertrand Gomes, José Eduardo |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2019 |
Fecha de depósito | 2022-05-16 |
Publicado en |
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Resumen | Purine homeostasis is ensured through a metabolic network widely conserved from prokaryotes to humans. Purines can either be synthesized de novo, reused, or produced by interconversion of extant metabolites using the ... Purine homeostasis is ensured through a metabolic network widely conserved from prokaryotes to humans. Purines can either be synthesized de novo, reused, or produced by interconversion of extant metabolites using the so-called recycling pathway. Although thoroughly characterized in microorganisms, such as yeast or bacteria, little is known about regulation of the purine biosynthesis network in metazoans. In humans, several diseases are linked to purine metabolism through as yet poorly understood etiologies. Particularly, the deficiency in adenylosuccinate lyase (ADSL)-an enzyme involved both in the purine de novo and recycling pathways-causes severe muscular and neuronal symptoms. In order to address the mechanisms underlying this deficiency, we established Caenorhabditis elegans as a metazoan model organism to study purine metabolism, while focusing on ADSL. We show that the purine biosynthesis network is functionally conserved in C. elegans. Moreover, adsl-1 (the gene encoding ADSL in C. elegans) is required for developmental timing, germline stem cell maintenance and muscle integrity. Importantly, these traits are not affected when solely the de novo pathway is abolished, and we present evidence that germline maintenance is linked specifically to ADSL activity in the recycling pathway. Hence, our results allow developmental and tissue specific phenotypes to be ascribed to separable steps of the purine metabolic network in an animal model. |
Agencias financiadoras | National Institutes of Health (NIH) Ministerio de Economía y Competitividad (MINECO). España |
Identificador del proyecto | P40 OD010440
U41 HG002223 RYC-2010-06167 RYC2014-15551 |
Cita | Marsac, R., Pinson, B., Saint-Marc, C., Olmedo López, M., Artal Sanz, M., Daignan-Fornier, B. y Gomes, J.E. (2019). Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans. Genetics, 211 (4), 1297-1313. |
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Purine Homeostasis.pdf | 1.682Mb | [PDF] | Ver/ | |