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  • In vivo analysis of Drosophila deoxyribonucleoside kinase function in cell cycle, cell survival and anti-cancer drugs resistance
    Piškur, Jure, 1960-2014
    In vitro studies have shown that Drosophila melanogaster has a highly efficient single deoxyribonucleoside kinase (dNK) multisubstrate enzyme. dNK is related to the mammalian Thymidine Kinase 2 (TK2) ... group involved in the nucleotide synthesis salvage pathway. To study the dNK function in vivo, we constructed transgenic Drosophila strains and impaired the nucleotide de novo synthesis pathway, using antifolates such as aminopterin. Our results show that dNK overexpression rescues both cell death and cell cycle arrest triggered by this anti-cancer drug, and confers global resistance on the fly. Moreover, we show that fly viability and growth depend on the exquisite ratio between dNK expression and its substrate thymidine (dT) in the medium, and that increased dT concentrations trigger apoptosis and a decrease in body masswhen dNK is mis-expressed. Finally, dNK expression, unlike that of TK2, iscell cycle dependent and under the control of CyclinE and the dE2F1 transcription factor involved in the G1/S transition. dNK is therefore functionally more closely related to mammalian TK1 than to TK2. This strongly suggests that dNK plays a role in cell proliferation in physiological conditions.
    Vir: Cell cycle. - ISSN 1538-4101 (Letn. 5, št. 7, 2006, str. 740-749)
    Vrsta gradiva - članek, sestavni del
    Leto - 2006
    Jezik - angleški
    COBISS.SI-ID - 25360089

vir: Cell cycle. - ISSN 1538-4101 (Letn. 5, št. 7, 2006, str. 740-749)
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