The Fanconi Anemia (FA) pathway is responsible for interstrand crosslink DNA repair []. The name originates the recessive syndrome known as Fanconi anemia, which causes developmental problems and cancer predisposition []. In this pathway, the FANCI-FANCD2 (ID) complex is ubiquitinated by the FA core complex and then travels to sites of damage to coordinate repair [, ]. FA pathway activation seems to trigger dissociation of FANCD2 from FANCI, coinciding with FANCD2 monoubiquitination which precedes monoubiquitination of FANCI []. This suggests a functional separation for FANCD2 from FANCI [].Monoubiquitinated FANCD2 functions to recruit DNA repair factors FAN1 (Fanconi-associated nuclease 1) []and SLX4 [], suggesting that chromatin-bound FANCD2Ub is a docking platform for certain DNA repair nucleases. FANCD2 has also a role in replication fork recovery [].
This family of proteins of unknown function gets its name from its position in the mammalian genome: Fanconi anemia group D2 protein opposite strand transcript protein.
Fanconi anemia (FA) is a human disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. This entry represents FANCG, which is part of the FA core complex required for the monoubiquitylation of FANCD2 and the FANCI heterodimer. The FA complex coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination []. Besides being part of the FA complex, FANCG also promotes formation of a protein complex containing BRCA2, FANCD2 and XRCC3 [].
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 [].
Fanconi anemia-associated protein of 24kDa (FAAP24) plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. It regulates FANCD2 monoubiquitination upon DNA damage. When repressed, it induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents. It targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA [].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 [, ].
Fanconi Anaemia (FA) is a cancer predisposition disorder characterised by chromosome fragility and hypersensitivity to genotoxic agents that suggest defects in the molecular mechanisms of DNA damage signalling and repair. In response to DNA damage, the FA core complex monoubiquitinates the FANCD2 protein. This ubiquitination targets FANCD2 to nuclear foci where it interacts with a variety of DNA repair proteins.The FA group E protein (FANCE) has an important role in DNA repair, functioning as the FANCD2-binding protein in the FA core complex []. This entry represents the C-terminal domain of FANCE, which consists predominantly of helices and does not contain any β-strands. This domain folds in a continuous right-handed solenoidal pattern from its N terminus to its C terminus.
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 [, ].This entry represents FANCC [].
FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) [].This entry represents the solenoid 1 cap (S1-cap) domain of the Fanconi anemia complementation group I protein (FANCI).
FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) [].This is the solenoid 1 (S1) domain of the Fanconi anemia group I protein (FANCI).
FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) [].This is the helical domain 1 (HD1) of the Fanconi anemia complementation group I protein (FANCI).
FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) [].This is the helical domain 2 (HD2) of the Fanconi anemia complementation group I protein (FANCI).
FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) [].This is the solenoid 3 (S3) domain of the Fanconi anemia group I protein (FANCI).
FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) [].This is the solenoid 4 (S4) domain of the Fanconi anemia group I protein (FANCI).
FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) [].This is the solenoid 2 (S2) domain of the Fanconi anemia group I protein (FANCI).
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 [, ].This entry represents FANCA [].
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 [, ].This entry represents the N-terminal domain of FANCA.
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 [, ].The FA group E protein (FANCE) has an important role in DNA repair, functioning as the FANCD2-binding protein in the FA core complex [].
FANCB (also known as FAAP95) is a component of the Fanconi anemia (FA) core complex []. The FA core complex mediates FANCD2 ubiquitination, a key activation step in the FA DNA damage response pathway [, , ]. The FANCB and the FA pathway also play a critical role in germ cell development []and in the maintenance of hematopoietic stem cell function [].FA is a recessive genetic disorder characterised by congenital abnormalities, progressive bone marrow failure and cancer susceptibility []. Eight proteins (FANCA, B, C, E, F, G, L and M) encoded by the FA causative genes have been demonstrated to form the FA nuclear core complex.
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.
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 [, ].
Fanconi anemia-associated protein of 100kDa (FAAP100) is component of the Fanconi anemia (FA) core complex, which plays a central role in FA-associated DNA damage response. FAAP100 is essential for the stability and function of the complex [].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 [, ].
Peptidase C19 contains ubiquitin hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquitinated peptides by cleavage of isopeptide bonds. They hydrolyze bonds involving the carboxyl group of the C-terminal Gly residue of ubiquitin. The purpose of the de-ubiquitination is thought to be editing of the ubiquitin conjugates, which could rescue them from degradation, as well as recycling of the ubiquitin. The ubiquitin/proteasome system is responsible for most protein turnover in the mammalian cell, and with over 50 members, family C19 is one of the largest families of peptidases in the human genome [, ].This entry encompasses ubiquitin-specific hydrolase 1 (MEROPS identifier C19.019). It is required for deubiquitination of monoubiquitinated proteins involved in various DNA repair pathways and is a key regulator of DNA repair mechanisms []. Substrates include monoubiquitinated PCNA [], and components FANCD2 []and FANCI []of the Fanconi anemia pathway, a genetic disorder that resultsin the inability to monoubiquitinate these components [].
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 [, ].Fanconi anemia group F protein (FANCF) is a component of the FA core complex [, ]. FANCF regulates its own expression by methylation at both mRNA and protein levels. Methylation-induced inactivation of FANCF has an important role on the occurrence of ovarian cancers by disrupting the FA-BRCA pathway [].This entry also includes homologues from plants.
