Fanconi anemia, complementation group E protein is a protein that in humans is encoded by the FANCEgene.[5][6][7] The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, and FANCL. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA cross-linking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation groufcrp E.[7]
Anuclear complex containing FANCE protein (as well as FANCC, FANCF and FANCG) is essential for the activation of the FANCD2 protein to the mono-ubiquitinated isoform.[8] In normal, non-mutant cells, FANCD2 is mono-ubiquinated in response to DNA damage. FANCE together with FANCC acts as the substrate adapter for this reaction [9] Activated FANCD2 protein co-localizes with BRCA1 (breast cancer susceptibility protein) at ionizing radiation-induced foci and in synaptonemal complexesofmeiotic chromosomes. Activated FANCD2 protein may function prior to the initiation of meiotic recombination, perhaps to prepare chromosomes for synapses, or to regulate subsequent recombination events.[8]
The main complex of FA contains a nuclear multi-subunit complex of notably 8 FA proteins.[12] This adds a single ubiquitin chain to the FANCD2 following DNA damage or duplicative pressure.[13]
For the collection of FANCC, FANCE is important in the nucleus and gathering of the core complex. Some characteristics of FANCE are that it can set itself up with ubiquitinated FANCD2, BRCA2 and constructed nuclear foci. Also, as it is the only member showing direct union with FANCD2 and gives the needed links between FA core complex and FANCD2.[14]
The structure of FANCE has an epitope on its surface that is found to be important for its binding with FANCD2. The existence of recurrent helical motif was not clear when analysis of amino acids was done.
It consists of 13 α-helices, 1 310-helix and no β-strand. Long shaped, non-globular shape and 70 Å n size. Width of 30 Å and thickness 20 Å. The protein folds continuously in right-handed manner from N- to C- terminal. Identifying it is easy because of its helices at the end of C-end.[14]
It restores DNA cross-links and is needed for nuclear accumulation of FANCC, delivering a critical bridge between FA complex and FANCD2.[15]
FANCE-deficient mice exhibit a reduced number of oocytes and disruption of prophase I of meiosis[16] indicating that FANCE has an essential role in meiosis.
FANCE has its application in Western Blot and IHC-P (Immunohistochemistry) where the predicted molecular weight was 58 kDa in Western blot and antigen recovery with citrate buffer pH6 was done before the onset of IHC-P.[15]
FANCE is also used in Gene Mapping, here homozygosity mapping, where it is fused with 3 DNA cells that will help in calculating the sensitivity to composites of Mitomycin C, a DNA cross-linking agent (Sigma). It also then examines the use of micro satellite markers D6S422 and D6S1610,[17] for linking. From this, a chromosomal region on chromosome 6p is located for FANCE.[17]
Immunoblotting showed that FANCE-L348M and FANCE-E263K mutants showed a division in the nuclear membrane of FA-E EUFA409 LCL indicating that irrespective of FANCE having putative nuclear localization signals,[18] it limits primarily to the nucleus.[19]
^Yin, H.; Suye, S.; Zhou, Z.; Cai, H.; Fu, C. (2022). "The reduction of oocytes and disruption of the meiotic prophase I in Fanconi anemia E-deficient mice". Reproduction. 164 (3): 71–82. doi:10.1530/REP-21-0421. PMID35671285. S2CID249432754.
^Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W (October 2003). "A novel ubiquitin ligase is deficient in Fanconi anemia". Nature Genetics. 35 (2): 165–70. doi:10.1038/ng1241. PMID12973351. S2CID10149290.
Wegner RD, Henrichs I, Joenje H, Schroeder-Kurth T (December 1996). "Fanconi anemia complementation group E: clinical and cytogenetic data of the first patient". Clinical Genetics. 50 (6): 479–82. doi:10.1111/j.1399-0004.1996.tb02716.x. PMID9147877. S2CID23242981.
Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W (October 2003). "A novel ubiquitin ligase is deficient in Fanconi anemia". Nature Genetics. 35 (2): 165–70. doi:10.1038/ng1241. PMID12973351. S2CID10149290.
