Monoubiquitination of FANCD2:FANCI

Stable Identifier
R-HSA-6785361
Type
Reaction [transition]
Species
Homo sapiens
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FANCD2 and FANCI, the components of the ID2 complex, are monoubiquitinated at DNA interstrand crosslinks (ICL-DNA) by the coordinated action of the E2 ubiquitin ligase UBE2T and the E3 ubiquitin ligase FANCL (Machida et al. 2006, Alpi et al. 2007, Sims et al. 2007, Smogorzewska et al. 2007, Longerich et al. 2009, Sato et al. 2012, Hodson et al. 2014). FANCL achieves the maximal catalytic activity as part of the ICL-DNA-bound FA core complex, and requires the presence of at least FANCB and FAAP100 subunits of the FA core complex to monoubiquitinate the ID2 complex (Rajendra et al. 2014, Longerich et al. 2014). FANCD2 is monoubiquitinated on lysine residue K561, while FANCI is monoubiquitinated on lysine residue K523 (Alpi et al. 2008, Longerich et al. 2014). In the absence of FANCD2, a DNA-bound FANCI can be monoubiquitinated in a FANCL-independent manner (Longerich et al. 2014).

UBE2T is also monoubiqutinated by FANCL on lysine residues K91 and K182 during the process of ID2 monoubiquitination. Monoubiquitination of UBE2T may serve as a self-inactivating mechanism that negatively regulates the Fanconi anemia pathway (Machida et al. 2006).

FANCD2 monoubiquitination promotes stability of the ID2 complex and its retention at ICL-DNA, and enables recruitment of additional proteins that participate in the repair of ICL-DNA (Garcia-Higuera et al. 2001, Smogorzewska et al. 2007, Alpi et al. 2008, Joo et al. 2011).

Literature References
PubMed ID Title Journal Year
19111657 Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI

Alpi, AF, Pace, PE, Babu, MM, Patel, KJ

Mol. Cell 2008
19589784 FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL

Longerich, S, San Filippo, J, Liu, D, Sung, P

J. Biol. Chem. 2009
17938197 UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination

Alpi, A, Langevin, F, Mosedale, G, Machida, YJ, Dutta, A, Patel, KJ

Mol. Cell. Biol. 2007
17412408 Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair

Smogorzewska, A, Matsuoka, S, Vinciguerra, P, McDonald ER, 3rd, Hurov, KE, Luo, J, Ballif, BA, Gygi, SP, Hofmann, K, D'Andrea, AD, Elledge, SJ

Cell 2007
11239454 Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway

Garcia-Higuera, I, Taniguchi, T, Ganesan, S, Meyn, MS, Timmers, C, Hejna, J, Grompe, M, D'Andrea, AD

Mol Cell 2001
24623813 Regulation of FANCD2 and FANCI monoubiquitination by their interaction and by DNA

Longerich, S, Kwon, Y, Tsai, MS, Hlaing, AS, Kupfer, GM, Sung, P

Nucleic Acids Res. 2014
22287633 DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI

Sato, K, Toda, K, Ishiai, M, Takata, M, Kurumizaka, H

Nucleic Acids Res. 2012
24905007 The genetic and biochemical basis of FANCD2 monoubiquitination

Rajendra, E, Oestergaard, VH, Langevin, F, Wang, M, Dornan, GL, Patel, KJ, Passmore, LA

Mol. Cell 2014
17460694 FANCI is a second monoubiquitinated member of the Fanconi anemia pathway

Sims, AE, Spiteri, E, Sims RJ, 3rd, Arita, AG, Lach, FP, Landers, T, Wurm, M, Freund, M, Neveling, K, Hanenberg, H, Auerbach, AD, Huang, TT

Nat Struct Mol Biol 2007
21764741 Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway

Joo, W, Xu, G, Persky, NS, Smogorzewska, A, Rudge, DG, Buzovetsky, O, Elledge, SJ, Pavletich, NP

Science 2011
16916645 UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation

Machida, YJ, Machida, Y, Chen, Y, Gurtan, AM, Kupfer, GM, D'Andrea, AD, Dutta, A

Mol Cell 2006
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Catalyst Activity
Title
ubiquitin protein ligase activity of p-FANCD2:p-FANCI:UBE2T:p-FA Core Complex:ICL-DNA [nucleoplasm]
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Orthologous Events
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