Department of Molecular, Cell and Cancer Biology
Cancer Biology | Cell Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetic Phenomena | Molecular Biology
Cells from Bloom's syndrome patients display genome instability due to a defective BLM and the downregulation of cytidine deaminase. Here, we use a genome-wide RNAi-synthetic lethal screen and transcriptomic profiling to identify genes enabling BLM-deficient and/or cytidine deaminase-deficient cells to tolerate constitutive DNA damage and replication stress. We found a synthetic lethal interaction between cytidine deaminase and microtubule-associated protein Tau deficiencies. Tau is overexpressed in cytidine deaminase-deficient cells, and its depletion worsens genome instability, compromising cell survival. Tau is recruited, along with upstream-binding factor, to ribosomal DNA loci. Tau downregulation decreases upstream binding factor recruitment, ribosomal RNA synthesis, ribonucleotide levels, and affects ribosomal DNA stability, leading to the formation of a new subclass of human ribosomal ultrafine anaphase bridges. We describe here Tau functions in maintaining survival of cytidine deaminase-deficient cells, and ribosomal DNA transcription and stability. Moreover, our findings for cancer tissues presenting concomitant cytidine deaminase underexpression and Tau upregulation open up new possibilities for anti-cancer treatment.Cytidine deaminase (CDA) deficiency leads to genome instability. Here the authors find a synthetic lethal interaction between CDA and the microtubule-associated protein Tau deficiencies, and report that Tau depletion affects rRNA synthesis, ribonucleotide pool balance, and rDNA stability.
DNA damage response, Nucleolus
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DOI of Published Version
Nat Commun. 2017 Sep 25;8(1):693. doi: 10.1038/s41467-017-00633-1. Link to article on publisher's site
Bou Samra E, Buhagiar-Labarchede G, Machon C, Guitton J, Onclercq-Delic R, Green MR, Alibert O, Gazin C, Veaute X, Amor-Gueret M. (2017). A role for Tau protein in maintaining ribosomal DNA stability and cytidine deaminase-deficient cell survival. Open Access Articles. https://doi.org/10.1038/s41467-017-00633-1. Retrieved from https://escholarship.umassmed.edu/oapubs/3264
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.