fanconi anemia complementation group a protein

Summary

Summary: A Fanconi anemia complementation group protein that is the most commonly mutated protein in FANCONI ANEMIA. It undergoes PHOSPHORYLATION by PROTEIN KINASE B and forms a complex with FANCC PROTEIN in the CELL NUCLEUS.

Top Publications

  1. Müller L, Milsom M, Kim M, Schambach A, Schuesler T, Williams D. Rapid lentiviral transduction preserves the engraftment potential of Fanca(-/-) hematopoietic stem cells. Mol Ther. 2008;16:1154-60 pubmed publisher
    ..Collectively, these data support the use of rapid lentiviral transduction for gene therapy in FA. ..
  2. Grompe M, D ANDREA A. Fanconi anemia and DNA repair. Hum Mol Genet. 2001;10:2253-9 pubmed
    ..Together, these data suggest that the FA pathway functions primarily as a DNA damage response system, although its exact role (direct involvement in DNA repair versus indirect, facilitating role) has not yet been defined. ..
  3. Callen E, Tischkowitz M, Creus A, Marcos R, Bueren J, Casado J, et al. Quantitative PCR analysis reveals a high incidence of large intragenic deletions in the FANCA gene in Spanish Fanconi anemia patients. Cytogenet Genome Res. 2004;104:341-5 pubmed
    ..Consequently, this technology should be applied in future studies on FANCA to improve the mutation detection rate. ..
  4. Hanenberg H, Batish S, Pollok K, Vieten L, Verlander P, Leurs C, et al. Phenotypic correction of primary Fanconi anemia T cells with retroviral vectors as a diagnostic tool. Exp Hematol. 2002;30:410-20 pubmed
    ..Phenotypic correction of FA T cells using retroviral vectors can be used successfully to determine the FA complementation group immediately after diagnosis of the disease. ..
  5. Otsuki T, Kajigaya S, Ozawa K, Liu J. SNX5, a new member of the sorting nexin family, binds to the Fanconi anemia complementation group A protein. Biochem Biophys Res Commun. 1999;265:630-5 pubmed
    ..Further studies are needed to elucidate the functional significance of FANCA and SNX5 binding; however, we speculate that FANCA may affect SNX5 traffic with cell surface receptors. ..
  6. Yuan F, Qian L, Zhao X, Liu J, Song L, D URSO G, et al. Fanconi anemia complementation group A (FANCA) protein has intrinsic affinity for nucleic acids with preference for single-stranded forms. J Biol Chem. 2012;287:4800-7 pubmed publisher
  7. Singh T, Bakker S, Agarwal S, Jansen M, Grassman E, Godthelp B, et al. Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood. 2009;114:174-80 pubmed publisher
    ..Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex-dependent and -independent manner. ..
  8. Medhurst A, Laghmani E, Steltenpool J, Ferrer M, Fontaine C, de Groot J, et al. Evidence for subcomplexes in the Fanconi anemia pathway. Blood. 2006;108:2072-80 pubmed
  9. Cohen Haguenauer O, Peault B, Bauche C, Daniel M, Casal I, Levy V, et al. In vivo repopulation ability of genetically corrected bone marrow cells from Fanconi anemia patients. Proc Natl Acad Sci U S A. 2006;103:2340-5 pubmed
    ..In addition, we provide a model of gene-corrected human primary cell growth that carries the potential to better delineate the combined role of both DNA damage and oxidative stress in the pathogenesis of FA. ..

More Information

Publications62

  1. Sobeck A, Stone S, Costanzo V, de Graaf B, Reuter T, de Winter J, et al. Fanconi anemia proteins are required to prevent accumulation of replication-associated DNA double-strand breaks. Mol Cell Biol. 2006;26:425-37 pubmed
  2. Yang Y, Herceg Z, Nakanishi K, Demuth I, Piccoli C, Michelon J, et al. The Fanconi anemia group A protein modulates homologous repair of DNA double-strand breaks in mammalian cells. Carcinogenesis. 2005;26:1731-40 pubmed
    ..These data identify the Fanca protein as an integral component in the early step of HDR of DSBs and thereby minimizing the genomic instability. ..
  3. Yamada K, Ramezani A, Hawley R, Ebell W, Arwert F, Arnold L, et al. Phenotype correction of Fanconi anemia group A hematopoietic stem cells using lentiviral vector. Mol Ther. 2003;8:600-10 pubmed
    ..Our results suggest that the lentiviral vector transduces stem cells capable of self-renewal and long-term hematopoiesis in vivo and is potentially useful for clinical gene therapy of FA hematopoietic cells. ..
  4. Reuter T, Medhurst A, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, et al. Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport. Exp Cell Res. 2003;289:211-21 pubmed
    ..Taken together, our data strongly support the hypothesis that FA proteins are functionally involved in several complex cellular pathways including transcription regulation, cell signaling, oxidative metabolism, and cellular transport. ..
  5. Hussain S, Witt E, Huber P, Medhurst A, Ashworth A, Mathew C. Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1. Hum Mol Genet. 2003;12:2503-10 pubmed
  6. Bouchlaka C, Abdelhak S, Amouri A, Ben Abid H, Hadiji S, Frikha M, et al. Fanconi anemia in Tunisia: high prevalence of group A and identification of new FANCA mutations. J Hum Genet. 2003;48:352-61 pubmed
    ..513G-->A in exon 5 and A-->G at position 166 (IVS24+166A-->G) of intron 24. Two new polymorphisms were also identified in intron 24 (IVS24-5G/A and IVS24-6C/G). ..
  7. Waisfisz Q, Morgan N, Savino M, de Winter J, van Berkel C, Hoatlin M, et al. Spontaneous functional correction of homozygous fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism. Nat Genet. 1999;22:379-83 pubmed
    ..Although in all three cases the predicted proteins were different from wild type, their cDNAs complemented the characteristic hypersensitivity of FA cells to crosslinking agents, thus establishing a functional correction to wild type. ..
  8. de Winter J, van Der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, et al. The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Hum Mol Genet. 2000;9:2665-74 pubmed
    ..Our results, along with published data, culminate in a model in which a multi-protein FA complex serves a nuclear function to maintain genomic integrity. ..
  9. D Andrea A, Grompe M. The Fanconi anaemia/BRCA pathway. Nat Rev Cancer. 2003;3:23-34 pubmed
  10. Qiao F, Moss A, Kupfer G. Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner. J Biol Chem. 2001;276:23391-6 pubmed
    ..Furthermore, phosphorylation of FancG was found to be temporally correlated with exit of the FA complex from chromosomes at mitosis. Taken together, these findings suggest a role for FA proteins in chromatin and nuclear matrix. ..
  11. Yamashita T, Nakahata T. Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes. Int J Hematol. 2001;74:33-41 pubmed
    ..Clarifying the molecular basis of this disease may provide new insights into the pathogenesis of bone marrow failure syndromes and myeloid malignancies. ..
  12. Sridharan D, Brown M, Lambert W, McMahon L, Lambert M. Nonerythroid alphaII spectrin is required for recruitment of FANCA and XPF to nuclear foci induced by DNA interstrand cross-links. J Cell Sci. 2003;116:823-35 pubmed
    ..These studies suggest that an important role for alphaSpIISigma* in the nucleus is to act as a scaffold, aiding in recruitment and alignment of repair proteins at sites of damage. ..
  13. van de Vrugt H, Koomen M, Bakker S, Berns M, Cheng N, van der Valk M, et al. Evidence for complete epistasis of null mutations in murine Fanconi anemia genes Fanca and Fancg. DNA Repair (Amst). 2011;10:1252-61 pubmed publisher
    ..The lack of an augmented phenotype suggest that null mutations in Fanca or Fancg are fully epistatic, making additional important functions outside of the FA core complex highly unlikely. ..
  14. Medhurst A, Huber P, Waisfisz Q, de Winter J, Mathew C. Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway. Hum Mol Genet. 2001;10:423-9 pubmed
    ..These proteins may act either as a multimeric complex or by sequential recruitment of subsets of the proteins in a common pathway that protects the genomic integrity of mammalian cells. ..
  15. Mankad A, Taniguchi T, Cox B, Akkari Y, Rathbun R, Lucas L, et al. Natural gene therapy in monozygotic twins with Fanconi anemia. Blood. 2006;107:3084-90 pubmed
    ..This finding suggests that treating FA patients with gene therapy might require transduction of only a few hematopoietic stem cells. ..
  16. Otsuki T, Furukawa Y, Ikeda K, Endo H, Yamashita T, Shinohara A, et al. Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex. Hum Mol Genet. 2001;10:2651-60 pubmed
  17. Benitez A, Yuan F, Nakajima S, Wei L, Qian L, Myers R, et al. Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein. Nucleic Acids Res. 2014;42:1671-83 pubmed publisher
    ..Intriguingly, ICL repair protein, Fanconi anemia complementation group A protein (FANCA), greatly enhances MUS81-EME1-mediated ICL incision...
  18. Noll M, Battaile K, Bateman R, Lax T, Rathbun K, Reifsteck C, et al. Fanconi anemia group A and C double-mutant mice: functional evidence for a multi-protein Fanconi anemia complex. Exp Hematol. 2002;30:679-88 pubmed
    ..These results support a model where both FANCA and FANCC are part of a multi-protein nuclear FA complex with identical function in cellular responses to DNA damage and germ cell survival. ..
  19. Wong J, Alon N, McKerlie C, Huang J, Meyn M, Buchwald M. Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia. Hum Mol Genet. 2003;12:2063-76 pubmed
    ..Taken together, our results suggest that the FA pathway plays a role in the maintenance of reproductive germ cells and in meiotic recombination. ..
  20. Meier D, Schindler D. Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements. PLoS ONE. 2011;6:e22911 pubmed publisher
    ..These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters. ..
  21. Hoskins E, Morris T, Higginbotham J, Spardy N, Cha E, Kelly P, et al. Fanconi anemia deficiency stimulates HPV-associated hyperplastic growth in organotypic epithelial raft culture. Oncogene. 2009;28:674-85 pubmed publisher
    ..Our findings support a new role for FA pathways in the maintenance of differentiation-dependent cell cycle exit, with the implication that FA deficiencies may contribute to the high risk of FA patients for developing HPV-associated SCC. ..
  22. Wang S, Bratti M, Rodriguez A, Herrero R, Burk R, Porras C, et al. Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer. J Infect Dis. 2009;199:20-30 pubmed publisher
    ..009). Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence. ..
  23. Sii Felice K, Barroca V, Etienne O, Riou L, Hoffschir F, Fouchet P, et al. Role of Fanconi DNA repair pathway in neural stem cell homeostasis. Cell Cycle. 2008;7:1911-5 pubmed
    ..Therefore, FA phenotype might be interpreted as a premature ageing of stem cells, DNA damages being among the driving forces of ageing. ..
  24. Li J, Sipple J, Maynard S, Mehta P, Rose S, Davies S, et al. Fanconi anemia links reactive oxygen species to insulin resistance and obesity. Antioxid Redox Signal. 2012;17:1083-98 pubmed publisher
    ..These findings establish a pathogenic and mechanistic link between ROS and insulin resistance in a unique human disease setting. ROS accumulation contributes to the insulin resistance in FA deficiency by targeting both PTP-? and PKR. ..
  25. Higuchi T, Koike K. [Fanconi's pancytopenia syndrome]. Nihon Rinsho. 2006;Suppl 3:418-21 pubmed
  26. Müller L, Milsom M, Harris C, Vyas R, Brumme K, Parmar K, et al. Overcoming reprogramming resistance of Fanconi anemia cells. Blood. 2012;119:5449-57 pubmed publisher
    ..These data define the role of the FA pathway in reprogramming and provide a strategy for future translational applications of patient-specific FA iPSCs. ..
  27. Larder R, Karali D, Nelson N, Brown P. Fanconi anemia A is a nucleocytoplasmic shuttling molecule required for gonadotropin-releasing hormone (GnRH) transduction of the GnRH receptor. Endocrinology. 2006;147:5676-89 pubmed
    ..We conclude that nucleocytoplasmic shuttling of FANCA is required for GnRH transduction of the alphaGSU and GnRHR gene promoters and propose that FANCA functions as a GnRH-induced signal transducer. ..
  28. Ben Yehoyada M, Wang L, Kozekov I, Rizzo C, Gottesman M, Gautier J. Checkpoint signaling from a single DNA interstrand crosslink. Mol Cell. 2009;35:704-15 pubmed publisher
    ..Repair occurs by both origin-dependent and origin-independent mechanisms. Our data suggest that cell sensitivity to crosslinking agents results from both checkpoint and DNA repair defects. ..
  29. Condie A, Powles R, Hudson C, Shepherd V, Bevan S, Yuille M, et al. Analysis of the Fanconi anaemia complementation group A gene in acute myeloid leukaemia. Leuk Lymphoma. 2002;43:1849-53 pubmed
    ..The data suggests that while FANCA mutations are rare, FANCA mutations may contribute to the development of the disease in a subset of AML. ..
  30. Sii Felice K, Etienne O, Hoffschir F, Mathieu C, Riou L, Barroca V, et al. Fanconi DNA repair pathway is required for survival and long-term maintenance of neural progenitors. EMBO J. 2008;27:770-81 pubmed publisher
    ..Our study demonstrates a critical role for Fanconi pathway in neural stem and progenitor cells during developmental and adult neurogenesis. ..
  31. Tamary H, Dgany O, Toledano H, Shalev Z, Krasnov T, Shalmon L, et al. Molecular characterization of three novel Fanconi anemia mutations in Israeli Arabs. Eur J Haematol. 2004;72:330-5 pubmed
    ..Further analysis of FA mutations will enable prenatal diagnosis and a rational therapeutic approach including frequent monitoring and early bone marrow transplantation. ..
  32. Rio P, Segovia J, Hanenberg H, Casado J, Martinez J, Göttsche K, et al. In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice. Blood. 2002;100:2032-9 pubmed
    ..More significantly, transductions with FANCA vectors corrected both the MMC hypersensitivity as well as the impaired ex vivo expansion ability that characterized the BM progenitors of Fanca(-/-) mice. ..
  33. Otsuki T, Nagashima T, Komatsu N, Kirito K, Furukawa Y, Kobayashi Si S, et al. Phosphorylation of Fanconi anemia protein, FANCA, is regulated by Akt kinase. Biochem Biophys Res Commun. 2002;291:628-34 pubmed
    ..Furthermore, phosphorylation of wild-type FANCA was blocked by coexpression of a constitutively active (CA)-Akt and enhanced by a dominant-negative (DN) Akt. Our results suggest that Akt is a negative regulator of FANCA phosphorylation. ..
  34. Hoskins E, Morreale R, Werner S, Higginbotham J, Laimins L, Lambert P, et al. The fanconi anemia pathway limits human papillomavirus replication. J Virol. 2012;86:8131-8 pubmed publisher
  35. Prieto Remón I, Sánchez Carrera D, López Duarte M, Richard C, Pipaon C. Elevated levels of STAT1 in Fanconi anemia group A lymphoblasts correlate with the cells' sensitivity to DNA interstrand crosslinking drugs. Haematologica. 2013;98:705-13 pubmed publisher
    ..Our data provide an explanation for the mixed sensitivity of Fanconi anemia group A cells to both genotoxic stress and inflammatory cytokines and indicate new targets for the treatment of bone marrow failure in these patients. ..
  36. Tischkowitz M, Morgan N, Grimwade D, Eddy C, Ball S, Vorechovsky I, et al. Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia. Leukemia. 2004;18:420-5 pubmed
    ..These findings suggest that gene deletions and reduced expression of FANCA may be involved in the promotion of genetic instability in a subset of cases of sporadic AML. ..
  37. Wilkes D, Sailer V, Xue H, Cheng H, Collins C, Gleave M, et al. A germline FANCA alteration that is associated with increased sensitivity to DNA damaging agents. Cold Spring Harb Mol Case Stud. 2017;3: pubmed publisher
  38. Capanni C, Bruschi M, Columbaro M, Cuccarolo P, Ravera S, Dufour C, et al. Changes in vimentin, lamin A/C and mitofilin induce aberrant cell organization in fibroblasts from Fanconi anemia complementation group A (FA-A) patients. Biochimie. 2013;95:1838-47 pubmed publisher
    ..FA-A cell appears structurally prone to physiologic stress and this could explain part of the phenotype of FA cells. ..
  39. Paiboonsukwong K, Ohbayashi F, Shiiba H, Aizawa E, Yamashita T, Mitani K. Correction of mutant Fanconi anemia gene by homologous recombination in human hematopoietic cells using adeno-associated virus vector. J Gene Med. 2009;11:1012-9 pubmed publisher
    ..The results obtained in the present study indicate that AAV vectors may be applicable for gene correction therapy of inherited hematopoietic disorders. ..
  40. Wong J, Alon N, Norga K, Kruyt F, Youssoufian H, Buchwald M. Cloning and analysis of the mouse Fanconi anemia group A cDNA and an overlapping penta zinc finger cDNA. Genomics. 2000;67:273-83 pubmed
    ..The overlapping genomic organization between Zfp276 and Fanca may have relevance to the disease phenotype of FA. ..
  41. Pulliam A, Hobson M, Ciccone S, Li Y, Chen S, Srour E, et al. AMD3100 synergizes with G-CSF to mobilize repopulating stem cells in Fanconi anemia knockout mice. Exp Hematol. 2008;36:1084-90 pubmed publisher
  42. Kuang Y, Garcia Higuera I, Moran A, Mondoux M, Digweed M, D Andrea A. Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity. Blood. 2000;96:1625-32 pubmed
    ..Additional amino acid sequences at the carboxy terminus of FANCG are required for the binding of FANCC in the complex. (Blood. 2000;96:1625-1632) ..
  43. Stone S, Sobeck A, van Kogelenberg M, de Graaf B, Joenje H, Christian J, et al. Identification, developmental expression and regulation of the Xenopus ortholog of human FANCG/XRCC9. Genes Cells. 2007;12:841-51 pubmed
    ..Our data demonstrate that interactions between FANCA and FANCG occur at the earliest stage of vertebrate development and raise the possibility that functionally different isoforms of xFANCG may play a role in early development. ..
  44. Zhu W, Dutta A. An ATR- and BRCA1-mediated Fanconi anemia pathway is required for activating the G2/M checkpoint and DNA damage repair upon rereplication. Mol Cell Biol. 2006;26:4601-11 pubmed
    ..In its absence, the cells rapidly lose viability when faced with rereplication. ..
  45. Levran O, Diotti R, Pujara K, Batish S, Hanenberg H, Auerbach A. Spectrum of sequence variations in the FANCA gene: an International Fanconi Anemia Registry (IFAR) study. Hum Mutat. 2005;25:142-9 pubmed
    ..In addition, a conserved SNP haplotype block spanning at least 60 kb of the FANCA gene was identified in individuals from various ethnic groups. ..
  46. Callen E, Casado J, Tischkowitz M, Bueren J, Creus A, Marcos R, et al. A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain. Blood. 2005;105:1946-9 pubmed
    ..The high carrier frequency makes the Spanish Gypsies a population model to study FA heterozygote mutations in cancer. ..
  47. van de Vrugt H, Koomen M, Berns M, de Vries Y, Rooimans M, van der Weel L, et al. Characterization, expression and complex formation of the murine Fanconi anaemia gene product Fancg. Genes Cells. 2002;7:333-42 pubmed
    ..Spleen, thymus and testis showed the highest Fancg expression levels. Although Fancg and Fanca are able to form a complex, this interaction is not required for Fancg to accumulate in the nuclear compartment. ..
  48. Yagasaki H, Hamanoue S, Oda T, Nakahata T, Asano S, Yamashita T. Identification and characterization of novel mutations of the major Fanconi anemia gene FANCA in the Japanese population. Hum Mutat. 2004;24:481-90 pubmed
    ..Specifically, our data suggest that diverse mechanisms including nonhomologous recombination as well as Alu-mediated homologous recombination are involved in the generation of large deletions in FANCA. ..
  49. Chandrasekharappa S, Lach F, Kimble D, Kamat A, Teer J, Donovan F, et al. Massively parallel sequencing, aCGH, and RNA-Seq technologies provide a comprehensive molecular diagnosis of Fanconi anemia. Blood. 2013;121:e138-48 pubmed publisher
    ..FANCC mutations are often the cause of FA in patients of Ashkenazi Jewish (AJ) ancestry, and we identified 2 novel FANCC mutations in 2 patients of AJ ancestry. We describe here a strategy for efficient molecular diagnosis of FA. ..
  50. Ravera S, Vaccaro D, Cuccarolo P, Columbaro M, Capanni C, Bartolucci M, et al. Mitochondrial respiratory chain Complex I defects in Fanconi anemia complementation group A. Biochimie. 2013;95:1828-37 pubmed publisher
    ..Electron microscopy measures indeed show profound alterations in mitochondrial ultrastructure and shape. ..
  51. Zheng Z, Geng J, Yao R, Li C, Ying D, Shen Y, et al. Molecular defects identified by whole exome sequencing in a child with Fanconi anemia. Gene. 2013;530:295-300 pubmed publisher
    ..989_995del, p.H330LfsX2) in FANCA gene. Our results indicate that whole exome sequencing may be useful in clinical settings for rapid identification of disease-causing mutations in rare genetic disorders such as Fanconi anemia. ..
  52. Mattioli C, Pianigiani G, De Rocco D, Bianco A, Cappelli E, Savoia A, et al. Unusual splice site mutations disrupt FANCA exon 8 definition. Biochim Biophys Acta. 2014;1842:1052-8 pubmed publisher
  53. Savino M, Borriello A, D Apolito M, Criscuolo M, Del Vecchio M, Bianco A, et al. Spectrum of FANCA mutations in Italian Fanconi anemia patients: identification of six novel alleles and phenotypic characterization of the S858R variant. Hum Mutat. 2003;22:338-9 pubmed
    ..The spectrum of FA mutations is widely in agreement with the heterogeneous ethnic origin of the Italian population. ..