Panoply™ Human MAPT Knockdown Stable Cell Line

Recent studies indicate that microtubules play a role in the repair of DNA double-strand breaks. This study investigated the function of the microtubule-associated protein Tau in the context of radiotherapy and chemotherapy. Tau was originally identified as a neuronal microtubule-associated protein (MAPT); its aggregation is a key pathogenic factor in neurodegenerative diseases such as Alzheimer's disease. Notably, reducing Tau expression in breast cancer cell lines led to a significant reduction in the volume of mouse breast cancer xenografts treated with doxorubicin or X-rays. Furthermore, Tau knockdown inhibited the classical non-homologous end joining (NHEJ) pathway and sensitized cells to bleomycin and X-rays. Mechanistic investigations revealed that Tau downregulation caused the retention of 53BP1 (p53-binding protein 1)-a key mediator of the DNA double-strand break response-in the cytoplasm. The study demonstrated that Tau facilitates the nuclear translocation of 53BP1 upon DNA damage by regulating microtubule-mediated transport. Additionally, Tau knockdown enhanced the sensitivity of cancer cells to DNA-adduct-forming chemotherapeutic agents such as cisplatin and oxaliplatin, suggesting a broader role for Tau in regulating the nuclear transport of DNA repair proteins. Collectively, these findings indicate that Tau expression levels in cancer cells may serve as a potential molecular biomarker for predicting cellular responses to DNA-damaging anticancer drugs.

Here, researchers examined the effect of Tau protein knockdown on the kinetics of double-strand break (DSB) clearance following a single dose of X-ray irradiation. MCF7 and MDA-MB-231 cell clones were exposed to 2 Gy of radiation, and the number of γ-H2AX foci was quantified at 5 minutes, 2 hours, 4 hours, and 6 hours post-irradiation. The results showed that the number of DSB foci increased approximately twofold in both control cells and Tau-knockdown MCF7 cells. However, in control cells, γ-H2AX foci levels began to decline after 2 hours and returned nearly to baseline levels by 6 hours; in contrast, levels in Tau-knockdown MCF7 cells remained unchanged throughout the 6-hour post-irradiation period (Figure 1A, C). Similar trends were observed in Tau-knockdown MDA-MB-231 cells and their corresponding control cells (Figure 1B, D).

Figure 1. Inhibition of Tau increases γ -H2AX levels after X-ray treatment in MCF7 and MDA-MB-231. (Rico T, et al., 2022)