Fig. 6
From: The novel phosphatase NUDT5 is a critical regulator of triple-negative breast cancer growth
Proposed mechanism of NUDT5 biological function in breast cancers. The level of ROS is low in ER-positive tumors, resulting in low accumulation of 8-oxoG and γH2AX lesions in the nucleus. In such cases, the inhibition or loss of NUDT5 does not affect the growth of these ER-positive tumors. In TNBC tumors, both ROS and NUDT5 levels are elevated. When NUDT5 is abundant, it mitigates oxidative DNA damage by hydrolyzing oxidized deoxyribonucleoside diphosphates. Consequently, there is no incorporation of 8-oxoG into the DNA, and γH2AX lesions do not accumulate. However, in the absence of NUDT5, uncontrolled oxidative stress on the nucleotide pool occurs. This leads to the incorporation of 8-oxoG lesions into the DNA and the accumulation of γH2AX lesions in the nucleus, ultimately causing DNA replication fork slowing and reduced proliferation