Monoubiquitination of FancD2

Stable Identifier
R-GGA-217150
Type
Reaction [transition]
Species
Gallus gallus
Compartment
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Fanconi anemia (FA) is a rare hereditary disorder characterized by bone marrow failure, compromised genomic stability and increased incidence of cancer. Thirteen complementation groups and genes have been identified, but the exact mechanistic function of many FA proteins remains unclear. FANCD1 is identified as the breast cancer susceptibility protein BRCA2 that is a key regulator of RAD5, having a central role in DNA repair mediated by homologous recombination . FANCD2 becomes monoubiquitinated at K563 in a reaction dependent on the FANCL-E3 ligase domain and localizes to subnuclear foci containing chromatin-associated BRCA1 and RAD51. This event is dependent on the functional FA core complex comprised of eight FA proteins (FANC A/B/C/E/F/G/L/M). Although BRCA2 is not required for ubiquitination, mono-ubiquitinated FANCD2,promotes IR-induced BRCA2 focus formation. Colocalization of FANCD2 and BRCA1along with RAD51 occurs during S phase, in response to double stranded breaks (DSBs) or exposure to drugs like mitomycin C (MMC) that induce DNA interstrand cross links (ICL). Thus the process of monoubiquitination of FANCD2 is an important event that connects the FA phenotype and HR pathways.

Literature References
PubMed ID Title Journal Year
12442171 Insights into DNA recombination from the structure of a RAD51-BRCA2 complex

Pellegrini, L, Yu, DS, Lo, T, Anand, S, Lee, M, Blundell, TL, Venkitaraman, AR

Nature 2002
12086603 Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways

Taniguchi, T, Garcia-Higuera, I, Xu, B, Andreassen, PR, Gregory, RC, Kim, ST, Lane, WS, Kastan, MB, D'Andrea, AD

Cell 2002
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
12531392 Cross-links between Fanconi anaemia and BRCA2

West, SC

DNA Repair (Amst) 2003
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ubiquitin-protein transferase activity of FancL [nucleoplasm]
Physical Entity
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