2024-03-29T13:42:59Zhttps://www.tdx.cat/oai/requestoai:www.tdx.cat:10803/3173862017-09-13T16:14:11Zcom_10803_369col_10803_83927
nam a 5i 4500
Cicle cel·lular
Ciclo celular
Cell cycle
Dany a DNA
Daño a DNA
DNA damage
dNTPs
Polifosfat
Polifosfato
Polyphosphate
S. cerevisiae
El polifosfat és un element clau durant la replicació del DNA.
[Barcelona] :
Universitat Internacional de Catalunya,
2015
Accés lliure
http://hdl.handle.net/10803/317386
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Bru Rullo, Samuel,
autor
1 recurs en línia (175 pàgines)
Tesi
Doctorat
Universitat Internacional de Catalunya. Departament de Ciències Bàsiques
2015
Universitat Internacional de Catalunya. Departament de Ciències Bàsiques
Tesis i dissertacions electròniques
Clotet Erra, Josep,
supervisor acadèmic
TDX
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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