DOI: 10.1101/509950Jan 2, 2019Paper

Fanconi anemia proteins are required to maintain nucleolar homeostasis.

BioRxiv : the Preprint Server for Biology
Anna GueiderikhFilippo Rosselli


The majority of inherited bone marrow failure (iBMF) syndromes are associated to nucleolar and/or ribosomal abnormalities, but Fanconi anemia (FA), the most common iBMF, is attributed to alterations in DNA damage responses. However, the involvement, if any, of the FA (FANC) proteins in the maintenance of nucleolar functions and/or ribosome biogenesis is yet unexplored. Here, we report that FANC pathway loss-of-function is associated to a loss of the nucleolar homeostasis, demonstrating increased rDNA rearrangements, accumulation of nucleolar DNA damage, nucleolar protein mislocalization, and a p53-independent induction of the growth inhibitory protein p21. Moreover, specifically associated to FANCA loss-of-function, which is responsible for approximately 65% of FA cases, we observed reduced rDNA transcription and rRNA processing as well as alteration in protein synthesis and polysome profiles. Thus, we have identified nucleolar consequences associated with FANC pathway deficiency, challenging current hypothesis on the physiopathology of FA.

Related Concepts

Bone Marrow
DNA Damage
Fanconi Anemia
Gene Rearrangement
Ribosomal RNA
Transcription, Genetic
Protein p53

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