1. Fanconi anemia protein FANCI functions in ribosome biogenesis.
- Author
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Sondalle SB, Longerich S, Ogawa LM, Sung P, and Baserga SJ
- Subjects
- Blotting, Western, Cell Nucleolus metabolism, DNA Repair physiology, Electrophoresis, Polyacrylamide Gel, Fanconi Anemia physiopathology, Fanconi Anemia Complementation Group Proteins genetics, Fanconi Anemia Complementation Group Proteins metabolism, HEK293 Cells, HeLa Cells, Humans, Mutation, Protein Biosynthesis, RNA Precursors genetics, RNA, Ribosomal genetics, Transcription, Genetic, Ubiquitination, Fanconi Anemia Complementation Group Proteins physiology, Ribosomes metabolism
- Abstract
Fanconi anemia (FA) is a disease of DNA repair characterized by bone marrow failure and a reduced ability to remove DNA interstrand cross-links. Here, we provide evidence that the FA protein FANCI also functions in ribosome biogenesis, the process of making ribosomes that initiates in the nucleolus. We show that FANCI localizes to the nucleolus and is functionally and physically tied to the transcription of pre-ribosomal RNA (pre-rRNA) and to large ribosomal subunit (LSU) pre-rRNA processing independent of FANCD2. While FANCI is known to be monoubiquitinated when activated for DNA repair, we find that it is predominantly in the deubiquitinated state in the nucleolus, requiring the nucleoplasmic deubiquitinase (DUB) USP1 and the nucleolar DUB USP36. Our model suggests a possible dual pathophysiology for FA that includes defects in DNA repair and in ribosome biogenesis., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
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