FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2

Maria Castella, Celine Jacquemont, Elizabeth L Thompson, Jung Eun Yeo, Ronald S. Cheung, Jen Wei Huang, Alexandra Sobeck, Eric A Hendrickson, Toshiyasu Taniguchi

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The Fanconi anemia (FA)-BRCA pathway mediates repair of DNA interstrand crosslinks. The FA core complex, a multi-subunit ubiquitin ligase, participates in the detection of DNA lesions and monoubiquitinates two downstream FA proteins, FANCD2 and FANCI (or the ID complex). However, the regulation of the FA core complex itself is poorly understood. Here we show that the FA core complex proteins are recruited to sites of DNA damage and form nuclear foci in S and G2 phases of the cell cycle. ATR kinase activity, an intact FA core complex and FANCM-FAAP24 were crucial for this recruitment. Surprisingly, FANCI, but not its partner FANCD2, was needed for efficient FA core complex foci formation. Monoubiquitination or ATR-dependent phosphorylation of FANCI were not required for the FA core complex recruitment, but FANCI deubiquitination by USP1 was. Additionally, BRCA1 was required for efficient FA core complex foci formation. These findings indicate that FANCI functions upstream of FA core complex recruitment independently of FANCD2, and alter the current view of the FA-BRCA pathway.

Original languageEnglish (US)
Article numbere1005563
JournalPLoS genetics
Volume11
Issue number10
DOIs
StatePublished - Jan 1 2015

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Fanconi Anemia
anemia
DNA damage
DNA Damage
DNA
damage
interphase
Fanconi Anemia Complementation Group Proteins
Fanconi anemia
G2 Phase
protein
Ligases
Ubiquitin
S Phase
DNA Repair
ubiquitin
DNA repair
ligases
lesion
Cell Cycle

Cite this

Castella, M., Jacquemont, C., Thompson, E. L., Yeo, J. E., Cheung, R. S., Huang, J. W., ... Taniguchi, T. (2015). FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2. PLoS genetics, 11(10), [e1005563]. https://doi.org/10.1371/journal.pgen.1005563

FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2. / Castella, Maria; Jacquemont, Celine; Thompson, Elizabeth L; Yeo, Jung Eun; Cheung, Ronald S.; Huang, Jen Wei; Sobeck, Alexandra; Hendrickson, Eric A; Taniguchi, Toshiyasu.

In: PLoS genetics, Vol. 11, No. 10, e1005563, 01.01.2015.

Research output: Contribution to journalArticle

Castella, Maria ; Jacquemont, Celine ; Thompson, Elizabeth L ; Yeo, Jung Eun ; Cheung, Ronald S. ; Huang, Jen Wei ; Sobeck, Alexandra ; Hendrickson, Eric A ; Taniguchi, Toshiyasu. / FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2. In: PLoS genetics. 2015 ; Vol. 11, No. 10.
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