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

The Genetic Instability and Carcinogenesis team (CNRS / Institut Curie/Paris Sud University) leaded by Mounira Amor-Guéret, in collaboration with researchers from CEA (Fontenay aux Roses, Evry), from « Les hospices civils de Lyon », and from the Howard Hugues Medical Institute (Massachusetts, USA), identified new functions for the Tau protein, as reported in the prestigious journal Nature Communications.

Representative immunofluorescence (IF) z‐projection images showing paired Tau foci (green) linked by PICH-positive UFBs in Bloom’s syndrome anaphase cells. Scale bar: 5 µm
Representative immunofluorescence (IF) z‐projection images showing paired Tau foci (green) linked by PICH-positive UFBs in Bloom’s syndrome anaphase cells. Scale bar: 5 µm

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 microtubuleassociated 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.”

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 & Mounira Amor-Guéret