Fanconi anemia (FA) is a human disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. The FA complex repairs the interstrand cross-linking (ICL) lesions and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. It is required for the monoubiquitylation of FANCD2 and FANCI heterodimer. The FA core complex consists of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FANCT (UBET2), FAAP100 and FAAP24 [, ].FANCL is an ubiquitin ligase that mediates monoubiquitination of FANCD2, a key step in the repair of interstrand DNA crosslinks (ICLs) in the Fanconi anemia (FA) pathway [, ]. In humans, defects in FANCL are the cause of Fanconi anemia complementation group L (FANCL). FANCL is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair [, ].
This entry represents the C-terminal domain of the FANCL, which is the E3 ubiquitin ligase subunit of the FA (Fanconi anaemia) complex [, , , ]. This entry represents the RING domain which recruits the UBE2T ubiquitin conjugating E2 enzyme as other RING E3s [, ].
This entry represents a region of approximately 100 residues containing three WD repeats and six cysteine residues- possibly as three cysteine-bridges associated with FancL.FancL is the ubiquitin ligase protein that mediates ubiquitination of FancD2, a key step in the DNA damage pathway [, ]. FancL belongs to the multisubunit Fanconi anemia (FA) complex, which is composed of subunits: FancA, FancB, FancC, FancE, FancF, FancG, FancL/PHF9 and FancM. The WD repeats are required for interaction of FancL with other subunits of the FA complex [].In humans defects in FancL are a cause of Fanconi anemia (FA) (OMIM:227650), and the FA complex is not found in FA patients. FA is a genetically heterogeneous, autosomal recessive disorder characterised by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
This entry represents the second of three UBC-like domains found in the FANCL protein, which is the catalytic E3 ubiquitin ligase subunit of the FA complex (Fanconi anaemia). Eight subunits encoded by the Fanconi anaemia gene products form a multisubunit nuclear complex which is required for mono-ubiquitination of a downstream FA protein, FANCD2 [, ].
This entry represents the third of three UBC-like domains found in the FANCL protein, which is the catalytic E3 ubiquitin ligase subunit of the FA complex (Fanconi anaemia). Eight subunits encoded by the Fanconi anaemia gene products form a multisubunit nuclear complex which is required for mono-ubiquitination of a downstream FA protein, FANCD2 [].
This superfamily represents the third of three UBC-like domains found in the FANCL protein, which is the catalytic E3 ubiquitin ligase subunit of the FA complex (Fanconi anaemia). Structurally, it consists of 3 alpha helices and 4 beta strands.FancL is the ubiquitin ligase protein that mediates ubiquitination of FancD2, a key step in the DNA damage pathway [, ]. FancL belongs to the multisubunit Fanconi anemia (FA) complex, which is composed of subunits: FancA, FancB, FancC, FancE, FancF, FancG, FancL/PHF9 and FancM. The WD repeats are required for interaction of FancL with other subunits of the FA complex [].In humans defects in FancL are a cause of Fanconi anemia (FA) (OMIM:227650), and the FA complex is not found in FA patients. FA is a genetically heterogeneous, autosomal recessive disorder characterised by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
Fanconi anemia complementation group I (FANCI) protein is a component of the Fanconi anemia DNA damage-response pathway []. The protein directly binds to a variety of DNA substrates []and plays an essential role in the repair of DNA double-strand breaks by homologous recombination. It is also involved in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL [].Defects in the FANCI gene are a cause of Fanconi anemia complementation group I []- a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
