A role for Tau protein in maintaining ribosomal DNA stability and cytidine deaminase-deficient cell survival

Elias Bou Samra, Géraldine Buhagiar-Labarchède, Christelle Machon, Jérôme Guitton, Rosine Onclercq-Delic, Michael R. Green, Olivier Alibert, Claude Gazin, Xavier Veaute and Mounira Amor-Guéret ()
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Elias Bou Samra: PSL Research University, UMR 3348
Géraldine Buhagiar-Labarchède: PSL Research University, UMR 3348
Christelle Machon: Centre Hospitalier Lyon-Sud
Jérôme Guitton: Centre Hospitalier Lyon-Sud
Rosine Onclercq-Delic: PSL Research University, UMR 3348
Michael R. Green: University of Massachusetts Medical School
Olivier Alibert: CEA-DRF-iRCM-LEFG-Genopole
Claude Gazin: CEA-DRF-iRCM-LEFG-Genopole
Xavier Veaute: CEA-DRF-iRCM-CIGEx
Mounira Amor-Guéret: PSL Research University, UMR 3348

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00633-1

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