Reactome | Monoubiquitination of FANCD2:FANCI

Monoubiquitination of FANCD2:FANCI

Stable Identifier

R-HSA-6785361

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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
19589784	FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL Longerich, S, Liu, D, San Filippo, J, Sung, P	J. Biol. Chem.	2009
19111657	Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI Alpi, AF, Patel, KJ, Babu, MM, Pace, PE	Mol. Cell	2008
17938197	UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination Patel, KJ, Mosedale, G, Dutta, A, Machida, YJ, Alpi, A, Langevin, F	Mol. Cell. Biol.	2007
17412408	Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair Smogorzewska, A, Elledge, SJ, Gygi, SP, Hurov, KE, D'Andrea, AD, Luo, J, McDonald ER, 3rd, Matsuoka, S, Vinciguerra, P, Hofmann, K, Ballif, BA	Cell	2007
11239454	Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway Taniguchi, T, Timmers, C, Ganesan, S, Garcia-Higuera, I, Meyn, MS, Hejna, J, D'Andrea, AD, Grompe, M	Mol Cell	2001
24623813	Regulation of FANCD2 and FANCI monoubiquitination by their interaction and by DNA Hlaing, AS, Tsai, MS, Longerich, S, Kwon, Y, Kupfer, GM, Sung, P	Nucleic Acids Res.	2014
22287633	DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI Kurumizaka, H, Ishiai, M, Toda, K, Takata, M, Sato, K	Nucleic Acids Res.	2012
24905007	The genetic and biochemical basis of FANCD2 monoubiquitination Rajendra, E, Patel, KJ, Wang, M, Dornan, GL, Passmore, LA, Oestergaard, VH, Langevin, F	Mol. Cell	2014
17460694	FANCI is a second monoubiquitinated member of the Fanconi anemia pathway Arita, AG, Sims, AE, Huang, TT, Lach, FP, Freund, M, Auerbach, AD, Sims RJ, 3rd, Hanenberg, H, Wurm, M, Landers, T, Neveling, K, Spiteri, E	Nat Struct Mol Biol	2007
21764741	Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway Elledge, SJ, Joo, W, Xu, G, Buzovetsky, O, Persky, NS, Pavletich, NP, Rudge, DG, Smogorzewska, A	Science	2011
16916645	UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation Gurtan, AM, Chen, Y, Machida, Y, Machida, YJ, Kupfer, GM, Dutta, A, D'Andrea, AD	Mol Cell	2006