<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs"^^ . "Telomeres cap chromosome ends and are essential for genome stability and human health, but they shorten in most human somatic cells with cell division due to the end replication problem. Telomerase a specialized reverse transcriptase that lengthens telomeres by adding GGTTAG repeats to chromosome ends and is upregulated in most human cancers to enable limitless proliferation. Here, we uncover two distinct mechanisms by which naturally occurring oxidized and therapeutic dNTP DNA precursors inhibit telomerase-mediated telomere elongation. We conducted a series of direct telomerase extension assays in the presence of modified dNTPs on various telomeric substrates. We provide direct evidence that telomerase can add the metabolized form of NRTIs, dideoxyadenosine 5’ triphosphate (ddITP) and 3’-azido-3’deoxythymidine triphosphate (AZT-TP), to the telomeric end, causing chain termination. In contrast, telomerase continues elongation after inserting oxidized 2-OH-dATP or the therapeutic 6-thioguanine metabolite, 6-thio-dGTP, but insertion disrupts translocation and inhibits further repeat addition. Kinetics reveal that telomerase poorly selects against 6-thio-dGTP, inserting with similar catalytic efficiency as dGTP. Furthermore, telomerase processivity factor POT1-TPP1 fails to restore processive elongation in the presence of inhibitory dNTPs. These findings reveal mechanisms for targeting telomerase with modified dNTPs in cancer therapy."^^ . "2021-01-19" . . . . . . . . "Samantha"^^ . "Sanford"^^ . "Samantha Sanford"^^ . . . . . . "Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs (PDF)"^^ . . . "ssanford dissertation final 12 17 20.pdf"^^ . . . "Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs (Other)"^^ . . . . . . "small.jpg"^^ . . . "Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #39981 \n\nMechanisms of telomerase inhibition by oxidized and therapeutic dNTPs\n\n" . "text/html" . .