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Semin Cancer Biol ; 94: 11-20, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37211293

RESUMEN

Reactive oxygen species (ROS) are common products of normal cellular metabolism, but their elevated levels can result in nucleotide modifications. These modified or noncanonical nucleotides often integrate into nascent DNA during replication, causing lesions that trigger DNA repair mechanisms such as the mismatch repair machinery and base excision repair. Four superfamilies of sanitization enzymes can effectively hydrolyze noncanonical nucleotides from the precursor pool and eliminate their unintended incorporation into DNA. Notably, we focus on the representative MTH1 NUDIX hydrolase, whose enzymatic activity is ostensibly nonessential under normal physiological conditions. Yet, the sanitization attributes of MTH1 are more prevalent when ROS levels are abnormally high in cancer cells, rendering MTH1 an interesting target for developing anticancer treatments. We discuss multiple MTH1 inhibitory strategies that have emerged in recent years, and the potential of NUDIX hydrolases as plausible targets for the development of anticancer therapeutics.


Asunto(s)
Nucleótidos , Hidrolasas Nudix , Monoéster Fosfórico Hidrolasas , Especies Reactivas de Oxígeno , Antineoplásicos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Enzimas Reparadoras del ADN , Nucleótidos/genética , Nucleótidos/metabolismo
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