El polifosfat és un element clau durant la replicació del DNA.
Throughout its lifespan, eukaryotic cells steadily consume free cytoplasmic orthophosphate to produce phospholipids and mRNA. However, during DNA synthesis, in a matter of minutes, cells require large amount of phosphate molecules to be incorporated in dNTPs. It is not known whether this high consum...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/317386 |
| Acesso em linha: | http://hdl.handle.net/10803/317386 |
| Access Level: | acceso abierto |
| Palavra-chave: | Cicle cel·lular Ciclo celular Cell cycle Dany a DNA Daño a DNA DNA damage dNTPs Polifosfat Polifosfato Polyphosphate S. cerevisiae Biologia 577 |
| Resumo: | Throughout its lifespan, eukaryotic cells steadily consume free cytoplasmic orthophosphate to produce phospholipids and mRNA. However, during DNA synthesis, in a matter of minutes, cells require large amount of phosphate molecules to be incorporated in dNTPs. It is not known whether this high consumption produces a sharp variation in cellular orthophosphate levels, or alternatively, a homeostatic system exists to prevent any variation. Polyphosphate (polyP) is a linear chain made of hundreds of Pi residues present in all living organisms, with a still unclear molecular function. In the present study we show that degradation of polyP is cell cycle regulated and, also, an important process to sustain the synthesis of dNTPs in S. cerevisiae. Mutants that cannot synthesise polyP (vtc4) or cannot hydrolyse it (ppn1 ppx1) present a lower rate of dNTP synthesis and it takes longer time to duplicate DNA. Recovery after UV stress also requires high levels of dNTPs, and here we show that mutants bearing low levels of polyP are more sensitive to UV, while cells overexpressing VTC4 are more resistant. Finally, we demonstrate that human dermal fibroblasts with reduced levels of polyP are also more sensitive to UV damage, suggesting that the protective role of polyP against UV damage might be conserved. In conclusion, this work identifies a new and important player during the synthesis of the building blocks of DNA. |
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