DUT, encoding deoxyuridine triphosphatase, is a key enzyme in nucleotide metabolism. It plays a crucial role in preventing uracil misincorporation during DNA replication, maintaining genomic stability. There are multiple isoforms in human cells, including nuclear (DUT-N), mitochondrial (DUT-M), DUT-3 without a localization signal, and DUT-4 with the same nuclear localization signal as DUT-N [2]. DUT-M is also involved in RLR-VISA-mediated antiviral signaling and mitochondrial metabolism [3].

In multiple myeloma, DUT knockdown by RNAi minimized bortezomib resistance, decelerated cell growth, and augmented apoptosis. In contrast, DUT overexpression enhanced resistance. DUT inhibition attenuated mitochondrial modulation and restricted MM progression [1]. In hepatocellular carcinoma, DUT knockout suppressed cell proliferation through cell cycle arrest and induced DNA damage. Targeting DUT's dUTPase activity with TAS-114 could suppress HCC growth and enhance sensitivity to Sorafenib [4].

In conclusion, DUT is essential for nucleotide metabolism and genomic stability. Its manipulation shows potential in treating multiple myeloma and hepatocellular carcinoma, highlighting the importance of DUT-related gene knockout models in understanding disease mechanisms and developing therapeutic strategies.