Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair.

By Agata Smogorzewska, S. Matsuoka, P. Vinciguerra, E. McDonald, Kristen E. Hurov, Ji Luo, Bryan A. Ballif, Steven P. Gygi, Kay Hofmann, A. D’Andrea and 1 more. Cell, 2007

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Fanconi anemia (FA) is a developmental and cancer-predisposition syndrome caused by mutations in genes controlling DNA interstrand crosslink repair. Several FA proteins form a ubiquitin ligase that controls monoubiquitination of the FANCD2 protein in an ATR-dependent manner. Here we describe the FA protein FANCI, identified as an ATM/ATR kinase substrate required for resistance to mitomycin C. FANCI shares sequence similarity with FANCD2, likely evolving from a common ancestral gene. The FANCI protein associates with FANCD2 and, together, as the FANCI-FANCD2 (ID) complex, localize to chromatin in response to DNA damage. Like FANCD2, FANCI is monoubiquitinated and unexpectedly, ubiquitination of each protein is important for the maintenance of ubiquitin on the other, indicating the existence of a dual ubiquitin-locking mechanism required for ID complex function. Mutation in FANCI is responsible for loss of a functional FA pathway in a patient with Fanconi anemia complementation group I.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/645439f184ee0337d6fee09ef40d5b1b412f351f

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Citations in the corpus

Maintaining genome stability at the replication fork (2010, background): “and ubiquitylates FANCI and FANCD2 , which constitute the group II protein”
The DNA Damage Response: Making it safe to play with knives (2010, background): “Moreover, FANCM has been suggested to associate with the BLM complex and also contribute to the activation of the ATR pathway at blocked replication forks (Collis et al., 2008; Deans and West, 2009; Huang et al., 2010; Schwab et al., 2010).”
A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. (2009, positive): “Recent advances in mammalian RNA interference (RNAi) technologies have made it possible to systematically interrogate the human genome for geneswhoselossoffunctionconstitutessyntheticlethalityeither with the oncogenic state or with particular oncogenic mutations (Ngo et al., 2006; Schlabach et al., ”
Regulation of DNA repair throughout the cell cycle (2008, background): “FA cells exhibit chromosome instability and increased sensitivity to DNA-crosslinking agents, which is indicative of a defect in DNA repair or recovery from blocked replication forks (see Ref”
DNA interstrand crosslink repair and cancer (2011, neutral): “ICLs that are induced during S phase activate the FA core complex to monoubiquitylate two further DNA-associated factors, FANCD2 and FANC”
A Proteome-wide, Quantitative Survey of In Vivo Ubiquitylation Sites Reveals Widespread Regulatory Roles (2011, background): “reported that monoubiquitylation of the Fanconi anemia (FA) pathway components FANCD2 and FANCI at K561 and K523, respectively, play important roles in DNA damage repair (41, 42).”
Mechanisms of DNA damage, repair and mutagenesis (2017, neutral): “In a yet unknown way, other FA core complex components (FANCA/B/C/ E/F/G/L/T) assemble at the damaged site and activate the phosphorylated FANCI–FANCD2 heterodimer through FANCL-mediated monoubiquitination [Smogorzewska et al., 2007].”