Fanconi anemia protein FANCI functions in ribosome biogenesis

Samuel B. Sondalle, Simonne Longerich, Lisa M. Ogawa, Patrick Sung, Susan J. Baserga

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2561-2570
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number7
DOIs
StatePublished - Feb 12 2019
Externally publishedYes

Keywords

  • FANCI
  • Fanconi anemia
  • Nucleolus
  • Pre-ribosomal RNA
  • Ribosome

ASJC Scopus subject areas

  • General

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