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

作者：Samra Elias Bou; Buhagiar Labarchede Geraldine; Machon Christelle; Guitton Jerome; Onclercq Delic Rosine; Green Michael R; Alibert Olivier; Gazin Claude; Veaute Xavier; Amor Gueret Mounira^*

来源：Nature Communications, 2017, 8(1): 693.

DOI：10.1038/s41467-017-00633-1

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.

• 出版日期2017-9-25
• 单位中国地震局