Abstract
Tau protein, traditionally recognized for stabilizing microtubules and forming pathological aggregates, has recently been observed to form condensates in various contexts. While its condensation with RNA has been well studied, the interaction between tau and DNA, along with its biological significance, remains less explored. Here, using single-molecule experiments, we find that tau binds stably to naked DNA at nanomolar concentrations, leading to the local co-condensation of tau and DNA. These tau condensates on DNA can also interface with microtubules, leveraging tau’s known role in promoting microtubule growth and organization. The dynamic nature of these condensates facilitates the remodeling of the DNA–microtubule assembly. Interestingly, phosphorylated tau and nucleosomal DNA exhibit distinct capacities to form condensates and recruit microtubules. Furthermore, imaging of mitotic cells with endogenous or exogenous tau reveals its localization to centromeres, engaging mitotic spindles, whereas expression of phosphomimetic tau mutants (T231D/S235D and S262D) causes defects in chromosome alignment. Building on these observations, we speculate that tau may play a role in mitosis, where tau clusters facilitate the early registration of mitotic spindles to chromosomes before kinetochore-mediated attachment. We also discuss the implications of this model in conditions where abnormal cell cycle re-entry and tau activity may disrupt cell division.
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Data availability
The RNA sequencing data are publicly available via NCBI BioProject accession number PRJNA1173100 (https://www.ncbi.nlm.nih.gov/sra/SRX26385062[accn]). Source data are provided as a Source Data file. All additional raw data files, including TIRF/confocal micrographs, are available from the corresponding author on request. Source data are provided with this paper.
Code availability
The code used for data analysis is available both at Github (https://github.com/ShonLab) and Zenodo (https://doi.org/10.5281/zenodo.17797566).
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Acknowledgements
We thank Jeong-Mo Choi, Cherlhyun Jeong, and Hajin Kim for helpful discussions; Euddeum E. Jeong, Gyu Ri Kim, Jiwon Jang, Sejoo Jeong, and Jong-Chan Lee for the help with cell imaging; Hee-Jung Jung for the help with mass spectrometry data analysis; Minkwon Cha, Sang-Hyeok Jeong, Surim Yoo, and Jiyoung Lee for the help with experiments; and the members of the Shon laboratory for discussions and assistance. We also thank UCRF (UNIST Central Research Facilities) for support in using the LC-MS/MS equipment; Gil-Yeol Ryu at the POSTECH Biotech Center for support with the Bio-TEM equipment. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2022R1C1C1012176 and RS-2024-00344154 to M.J.S.; RS-2023–00218927 to J.-B.L., J.-H.J., M.J.S., and Y.K.; 2022R1C1C1005378 to Y.K.) and by POSTECH Basic Science Research Institute Grant (RS-2021-NR060139 to M.J.S.).
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M.J.S. conceived the project. C.P., J.J., Y.H., D.S.H., and M.J.S. designed the experiments. C.P., J.J., Y.H., H.Y., K.Y., J.Y.B., S.-H.R., C.L.-E., and M.S. prepared all samples. C.P. performed TIRF imaging and microtubule experiments. J.J., J.Y.B., and S.-H.R. performed magnetic tweezers experiments. J.J. and H.Y. conducted confocal imaging and bulk LLPS experiments. K.Y. conducted skybridge experiments, and J.S. analyzed the results. A.J. and S.H. performed RNA sequencing and analysis. M.K. with C.L. ran tau–DNA binding simulations and analyzed the results, and J.-H.J. oversaw data analysis. M.J.S., D.S.H., J.-B.L., J.-H.J., and Y.K. supervised the study. C.P., J.J., H.Y., J.S., S.H., K.Y., M.K., and C.L. prepared figures and drafted the initial manuscript. M.J.S., C.P., and J.J. wrote and edited the final manuscript with contributions from all authors.
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Park, C., Jung, J., Hong, Y. et al. Tau condensation on DNA mediates microtubule attachment suggesting a mitotic role for centromere-localized tau. Nat Commun (2026). https://doi.org/10.1038/s41467-025-67888-x
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DOI: https://doi.org/10.1038/s41467-025-67888-x
