Adefovir dipivoxil induces DNA replication stress and augments ATR inhibitor‐related cytotoxicity
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چکیده
منابع مشابه
Cytotoxicity of pivoxil esters of antiviral acyclic nucleoside phosphonates: adefovir dipivoxil versus adefovir.
Biological effectiveness of antiviral acyclic nucleoside phosphonate adefo vir, 9-[2-(phosphonomethoxy)ethy]ade nine (PMEA) and its more lipophilic (bis)pivaloyloxymethyl ester prodrug adefovir dipivoxil (bis-POM-PMEA) were compared under in vitro conditions in mammalian cell systems. Proliferation of murine splenocytes was inhibited in a concentration-dependent manner, the bis-POM-PMEA being m...
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ATR is an essential kinase activated in response to DNA-replication stress, with a known target being the RPA2 subunit of human replication protein A (RPA). We find that S33-RPA2 phosphorylation by ATR occurs primarily in the late-S and G2 phases, probably at sites of residual stalled DNA-replication forks, with S33-P-RPA2 contained within nuclear repair centers. Although cells in which endogen...
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DNA replication stress is an inefficient DNA synthesis process that leads replication forks to progress slowly or stall. Two main factors that cause replication stress are alterations in pools of deoxyribonucleotide (dNTP) precursors required for DNA synthesis and changes in the activity of proteins required for synthesis of dNTPs. Ribonucleotide reductase (RNR), containing regulatory hRRM1 and...
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ژورنال
عنوان ژورنال: International Journal of Cancer
سال: 2020
ISSN: 0020-7136,1097-0215
DOI: 10.1002/ijc.32966