RESUMEN
Adequate dietary intake of essential metals such as zinc is important for maintaining homeostasis. Abnormal zinc intake in Caenorhabditis elegans has been shown to increase or decrease normal lifespan by influencing the insulin/IGF-1 pathway. Distribution of zinc is achieved by a family of highly conserved zinc transport proteins (ZIPT in C. elegans). This study investigated the role of the zipt family of genes and showed that depletion of individual zipt genes results in a decreased lifespan. Moreover, zipt-16 and zipt-17 mutants synthetically interact with the insulin/IGF cofactors daf-16 and skn-1, and cause abnormal localisation of DAF-16. This study suggests that the zipt family of genes are required for maintaining normal lifespan through influencing the insulin/IGF-1 pathway.
Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiología , Proteínas Portadoras/metabolismo , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Insulina/metabolismo , Longevidad/fisiología , Animales , Animales Modificados Genéticamente , Proteínas de Caenorhabditis elegans/genética , Proteínas Portadoras/genética , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , MutaciónRESUMEN
GCNA proteins are expressed across eukarya in pluripotent cells and have conserved functions in fertility. GCNA homologs Spartan (DVC-1) and Wss1 resolve DNA-protein crosslinks (DPCs), including Topoisomerase-DNA adducts, during DNA replication. Here, we show that GCNA mutants in mouse and C. elegans display defects in genome maintenance including DNA damage, aberrant chromosome condensation, and crossover defects in mouse spermatocytes and spontaneous genomic rearrangements in C. elegans. We show that GCNA and topoisomerase II (TOP2) physically interact in both mice and worms and colocalize on condensed chromosomes during mitosis in C. elegans embryos. Moreover, C. elegans gcna-1 mutants are hypersensitive to TOP2 poison. Together, our findings support a model in which GCNA provides genome maintenance functions in the germline and may do so, in part, by promoting the resolution of TOP2 DPCs.